summary of the steps of protein synthesis

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Protein Synthesis

Reviewed by: BD Editors

Protein synthesis is process in which polypeptide chains are formed from coded combinations of single amino acids inside the cell. The synthesis of new polypeptides requires a coded sequence, enzymes, and messenger, ribosomal, and transfer ribonucleic acids (RNAs). Protein synthesis takes place within the nucleus and ribosomes of a cell and is regulated by DNA and RNA.

Protein Synthesis Steps

Protein synthesis steps are twofold. Firstly, the code for a protein (a chain of amino acids in a specific order) must be copied from the genetic information contained within a cell’s DNA. This initial protein synthesis step is known as transcription.

Transcription produces an exact copy of a section of DNA. This copy is known as messenger RNA (mRNA) which must then be transported outside of the cell nucleus before the next step of protein synthesis can begin.

The second protein synthesis step is translation. Translation occurs within a cell organelle called a ribosome. Messenger RNA makes its way to and connects with the ribosome under the influence of ribosomal RNA and enzymes. Transfer RNA (tRNA) is a molecule that carries a single amino acid and a coded sequence that acts like a key. This key fits into a specific sequence of three codes on the mRNA, bringing the correct amino acid into place. Each set of three mRNA nitrogenous bases is called a codon.

Translation and transcription will be explained in much more detail further on. In order to keep protein synthesis simple, we first need to know the basics.

Polypeptides and Proteins

The result of protein synthesis is a chain of amino acids that have been attached, link by link, in a specific order. This chain is called a polymer or polypeptide and is constructed according to a DNA-based code. You can picture a polypeptide chain as a string of beads, with each bead playing the part of an amino acid. The order in which the beads are strung are copied from instructions in our DNA.

When speaking of protein synthesis it is important to make a distinction between polypeptide chains and proteins. All proteins are polypeptides but not all polypeptides are proteins; however, both proteins and polypeptides are composed of amino acid monomers.

The difference between a protein and a polypeptide is the form. Smaller chains of amino acids – usually less than forty – remain as single-chain strands and are called polypeptides. Larger chains must package themselves more tightly; they fold into fixed structures – secondary, tertiary, and quaternary. When a polypeptide chain folds, it is called a protein.

Polypeptide chains are formed during the translation process of protein synthesis. These polypeptides may or may not fold into proteins at a later stage. However, the term ‘protein synthesis’ is used even in the scientific community and is not incorrect.

Understanding protein synthesis is easy when we imagine our DNA as a recipe book. This book lists the instructions that show a cell how to make every tiny part of every system, organ, and tissue within our bodies. All of these individual parts are polypeptides. From the keratin in your hair and fingernails to the hormones that run through your bloodstream, polypeptides and proteins are the foundation stones of every structure. Our DNA does not code for lipids or carbohydrates – it only codes for polypeptides.

The enzyme RNA polymerase opens the DNA recipe book that sits inside the cell nucleus. It uses certain pieces of code as bookmarks to find the right page. This recipe book is written in a foreign language – mRNA copies what is written without understanding it. The recipes are translated into a language that other molecules can decipher at a later stage. The translators are ribosomes and tRNA. They read the recipe and can collect the right ingredients and, in the correct order, make the finished polypeptide product.

DNA Sequences

In the nucleus, two strands of DNA are held together by nitrogenous bases (also called nucleobases or bases). Four bases  – cytosine, guanine, adenine, and thymine – form the letters of the words in the DNA recipe book.

One strand of DNA holds the original code. If the instructions of this code are carefully followed, a specific correct polypeptide can be assembled outside the nucleus. The second DNA strand – the template strand – is a mirror image of the original strand. It must be a mirror image as nucleobases can only attach to complementary partners. For example, cytosine only ever pairs with guanine and thymine only pairs with adenine.

You will probably have seen codes such as CTA, ATA, TAA, and CCC in various biology textbooks. If these are the codons (sets of three bases) of the original strand of DNA, the template strand will attach to these using their partners. So using the given examples, template DNA will attach to the original DNA strand using GAT, TAT, ATT, and GGG.

Messenger RNA then copies the template strand. This means it ends up creating an exact copy of the original strand. The only difference is that mRNA replaces thymine with a base called uracil. The mRNA copy of the template strand using the given examples would read CUA, AUA, UAA, and CCC.

These codes can be read by transfer RNA outside the nucleus; the recipe can be understood by a molecule that does not fully understand the language used in the original (it does not understand thymine, only uracil). Transfer RNA helps to bring the right parts to the assembly line of the ribosome. There, a protein chain is constructed that matches the instructions in the original DNA strand.

Protein Synthesis Contributors

To make the copied stretch of code (transcription) we need enzymes called RNA polymerases. These enzymes gather free-floating messenger RNA (mRNA) molecules inside the nucleus and assemble them to form the letters of the code. Each letter of DNA code has its own key and each new letter formed by mRNA carries a lock that suits this key, a little like tRNA.

Notice that we are talking about letters. This is important. Inside the nucleus, the DNA code is not understood, simply copied down – transcribed. Understanding the code by spelling out the words formed by these letters  – translating – happens at a later stage.

RNA polymerase must find and bring over the appropriate mRNA molecule for each nitrogenous base on the template strand. Selected mRNA molecules link together to form a chain of letters. Eventually, these letters will spell out the equivalent of a phrase. Each phrase represents a specific (polypeptide) product. If the recipe is not exactly followed, the final product might be completely different or not work as well as it should.

Messenger RNA has now become the code. It travels to the next group of important contributors that work as manufacturing plants. Ribosomes are found outside the cell nucleus, either in the cell cytoplasm or attached to the rough endoplasmic reticulum; it is ribosomes that make the endoplasmic reticulum ‘rough’.

A ribosome is split into two parts and the strand of mRNA runs through it like ribbon through an old-fashioned typewriter. The ribosome recognizes and connects to a special code at the start of the translated phrase – the start codon. Transfer RNA molecules enter the ribosome, bringing with them individual ingredients. As with all of these processes, enzymes are required to make the connections.

If each mRNA codon has a lock, tRNA possesses the keys. The tRNA key for an mRNA codon is called an anticodon. When a tRNA molecule holds the key that matches a three-nucleobase code it can open the door, drop off its load (an amino acid), and leave the ribosome factory to collect another amino acid load. This will always be the same type of amino acid as the anticodon.

Messenger RNA shifts along the ribosome as if on a conveyor belt. At the next codon another tRNA molecule (with the right key) brings the next amino acid. This amino acid bonds to the previous one. A chain of bonded amino acids begins to form– a polypeptide chain. When completed, this polypeptide chain is an accurate final product manufactured according to the instructions in the DNA recipe book. Not a pie or a cake but a polypeptide chain.

The end of the mRNA code translation process is signaled by a stop codon. Start and stop codons do not code for amino acids but tell the tRNA and ribosome where a polypeptide chain should begin and end.

The finished product – the newly synthesized polypeptide – is released into the cytoplasm. From there it can travel to wherever it is needed.

Site of Protein Synthesis

The site of protein synthesis is twofold. Transcription (copying the code) occurs within the cell nucleus where DNA is located. Once the mRNA copy of a small section of DNA has been made it travels through the nuclear pores and into the cell cytoplasm. In the cytoplasm, the strand of mRNA will move towards a free ribosome or one attached to the rough endoplasmic reticulum. Then the next step of protein synthesis – translation – can begin.

New Roles for Ribosomes

The average mammalian cell contains more than ten million ribosomes. Cancer cells can produce up to 7,500 ribosomal subunits (small and large) every minute. As a polypeptide-producing factory, the existence, development, and function of every living organism depends on the ribosome.

It was previously thought that eukaryotic ribosomes only played effector roles in protein synthesis (caused an effect – a new protein). However, recent research now shows that ribosomes also regulate the translation process. They play a part in deciding which proteins are manufactured and in what quantities. The success and results of translation depend on more than the availability of free amino acids and enzymes  – they also depend on the quality of the ribosomes.

Transcription in Protein Synthesis

The transcription process is the first step of protein synthesis. This step transfers genetic information from DNA to the ribosomes of the cytoplasm or rough endoplasmic reticulum. Transcription is divided into three phases: initiation, elongation and termination.

Initiation requires two special protein groups. The first group is transcription factors – these recognize promoter sequences in the DNA. A promoter sequence is a section of code found at the start of a single gene that shows where the copying process should begin and in which direction this code should be read. A promoter works a little like the start codon on mRNA.

The second protein group necessary for transcription initiation consists of DNA-dependent RNA polymerases (RNAPs). An RNA polymerase molecule binds to the promoter. Once this connection has been made, the double-stranded DNA unwinds and opens (unzips).

Connected bases keep the two strands of DNA in a double-helix form. When the two strands unzip, the individual and now unpartnered bases are left exposed. The unzipping process is repeated along the stretch of DNA by RNAPs until the transcription stop point or terminator is reached. Intitiation, therefore, involves the recognition of a promotor sequence and the unzipping of a section of DNA under the influence of transcription factors and RNA polymerases.

The next phase in the transcription process is elongation. With the coded sequence exposed, RNAPs can read each individual adenine, guanine, cytosine, or thymine base on the template strand and connect the correct partner base to it. It is important to remember that RNA is unable to replicate thymine and replaces this with the nucleobase known as uracil.

If, for example, a short DNA sequence on the template strand is represented by C-A-G-T-T-A or cytosine-adenine-guanine-thymine-thymine-adenine, RNAP will connect the correct partner bases obtained from populations of free-floating bases within the nucleus. In this example, RNA polymerase will attach a guanine base to cytosine, uracil to adenine, cytosine to guanine, and adenine to thymine to form a strand of messenger RNA with the coded nitrogenous base sequence G-U-C-A-A-U. This process repeats until the RNAP enzyme detects a sequence of genetic code that terminates it – the terminator.

Termination

When the RNAPs detect a terminator sequence, the final phase of transcription – termination – takes place. The string of RNAPs disconnect from the DNA and the result is a strand of messenger RNA. This mRNA carries the code that will eventually instruct tRNA which amino acids to bring to a ribosome.

Messenger RNA leaves the nucleus via nuclear pores primarily through diffusion but sometimes needs help from transporter enzymes and ATP to reach its destination.

Translation Process in Protein Synthesis

During the translation process, the small and large subunits of a ribosome close over a strand of mRNA, trapping it loosely inside. Ribosomes arrange the strand into codons or sets of three nitrogenous base letters. This is because the code for a single amino acid – the most basic form of a protein – is a three-letter nucleobase code.

As ribosomes recognize parts of code, we can say they understand it. The jumble of copied letters made during the transcription phase can be read and understood in the translation phase.

For example, GGU, GGC, GGA, and GGG code for the amino acid known as glycine. Most amino acids have multiple codes as this lowers the chance of mistakes – if RNA polymerase accidently connects adenine instead of cytosine to GG, it doesn’t matter. Both GGC and GGA code for the same amino acid. You can see a list of mRNA codons for the twenty non-essential amino acids here .

There is only one start codon code –  AUG. Three codons – TAA, TAG, and TGA – represent stop codons. Neither start nor stop codons match the code for an amino acid; they are non-coding. The single start and three stop codons are clearly marked on this codon wheel.

When a codon becomes visible – once the previous codon has been linked to an amino acid – a section of a transfer RNA molecule fits into the mRNA codon. This ‘key’ is called the anticodon. Transfer RNA has two roles – to attach to an amino acid outside of the ribosome and to deploy this amino acid at the right time and in the right position on an mRNA strand within the ribosome.

Tens to thousands of transfer RNA molecules produce a polypeptide chain. Titin or connectin is the largest protein molecule and contains around 33,000 amino acids. The smallest functional polypeptide is glutathione – just three amino acids. To produce glutathione, first the ribosome and tRNA must read the start codon (three bases), then read the first protein-coding codon (three bases), the second (three bases), the third (three bases), and the stop codon (three bases). The coding DNA and mRNA recipes (sequences) for glutathione contain nine bases. There may or may not be additional sections of non-coding DNA within this recipe. Non-coding sequences do not produce amino acids .

As with the process of transcription, translation within the ribosome is also split into the three stages of initiation, elongation, and termination.

Initiation involves the recognition by the ribosome of the mRNA start codon. Elongation refers to the process whereby the ribosome moves along the mRNA transcript, recognizing and exposing individual codons so that tRNA can bring the right amino acids. The anticodon arm of tRNA attaches to the appropriate mRNA codon under the influence of ribosomal enzymes.

Finally, termination occurs when the ribosome recognizes the mRNA stop codon; the completed polypeptide chain is then released into the cytoplasm. It is sent wherever it is needed – inside the cell or to other tissues, exiting the cell membrane via exocytosis.

1. What are promotor sequences?

2. Which mRNA nitrogenous base is partner to the DNA base adenine?

3. RNAPs do what during translation initiation?

4. How many amino acids make up the protein glutathione?

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Bibliography

• Barna M. (2013). Ribosomes take control. Proceedings of the National Academy of Sciences of the United States of America , 110 (1), 9–10. https://doi.org/10.1073/pnas.1218764110
• Hatfield DL, Lee JL, Pirtle RM (Ed). (2018). Transfer RNA in Protein Synthesis.Boca Raton (FL), CRC Press.
• Rodwell, VW, Bender DA, Botham KM, Kennelly PJ, Weil PA. (2018). Harper’s Illustrated Biochemistry Thirty-First Edition. New York, McGraw Hill Professional.
• Vargas DY, Raj A, Marras SAE, Kramer FR, Tyagi S. (2005). Mechanism of mRNA transport in the nucleus. Proceedings of the National Academy of Sciences . Nov 2005, 102 (47) 17008-17013; DOI: 10.1073/pnas.0505580102

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Protein Synthesis

Protein synthesis, as the name implies, is the process by which every cell produces specific proteins in its ribosome. In this process, polypeptide chains are formed from varying amounts of 20 different amino acids. It is one of the fundamental biological processes in both prokaryotes and eukaryotes. This is a vital process, as the proteins formed take part in every major cellular activities, ranging from catalysis to forming various structural elements of the cell.

In 1958, Francis Crick proposed a theory called central dogma to describe the flow of genetic information from DNA to RNA to protein. According to this framework, protein is formed from RNA via translation , which in turn, is formed from DNA through transcription.

DNA → RNA → Protein

i. DNA → RNA (Transcription)

ii. RNA → Protein (Translation)

Where and When does Protein Synthesis Take Place

In both prokaryotes and eukaryotes, protein synthesis occurs in the ribosome. That’s why the ribosome is called the ‘protein factory’ of the cell.

However, in eukaryotes , the ribosomes remain scattered in the cytoplasm and are also attached to the Endoplasmic reticulum (RER). So, generally, it is said that, in eukaryotes, the process occurs in the cytoplasm and RER.

On the other hand, in prokaryotes , the ribosomes are scattered throughout the cell cytoplasm. So, commonly, it is said that, in prokaryotes, it takes place in the cytoplasm.

Process: How does it Work

The process of protein synthesis occurs in two steps: transcription and translation. In the first step, DNA is used as a template to make a messenger RNA molecule (mRNA). The mRNA thus formed, exits the nucleus through a nuclear pore and travels to the ribosome for the next step, translation. Upon reaching the ribosome, the genetic code in mRNA is read and used for polypeptide synthesis.

Below is a flowchart of the overall process:

Now, let us discuss these two steps of protein synthesis in detail:

1) Transcription: The First Step of Protein Synthesis

In this process, a single-stranded mRNA molecule is transcribed from a double-stranded DNA molecule. The mRNA thus formed is used as a template for the next step, translation.

The three steps of transcription are: initiation, elongation, and termination.

i) Initiation

The process of transcription begins when the enzyme RNA polymerase binds to a region of a gene called the promoter sequence with the assistance of certain transcription factors. Due to this binding, the double-stranded DNA starts to unwind at the promoter region, forming a transcription bubble. Among the two strands of DNA, one that is used as a template to produce mRNA is called the template, noncoding, or antisense strand. On the other hand, the other one is called the coding or sense strand.

ii) Elongation

After the opening of DNA, the attached RNA polymerase moves along the template strand of the DNA, creating complementary base pairing of that strand to form mRNA. As a result of this, an mRNA transcript containing a copy of the coding strand of DNA is formed. The only exception is, in the mRNA, the nitrogenous base thymine gets replaced by uracil. The sugar-phosphate backbone forms through RNA polymerase.

iii) Termination

Once the mRNA strand is complete, the hydrogen bonds between the RNA-DNA helix break. As a result, the mRNA detaches from the DNA and undergoes further processing.

Post Transcriptional Modification: mRNA Processing

The mRNA formed at the end of the transcription process is called pre-mRNA, as it is not fully ready prepared to enter translation. So, before leaving the nucleus, it needs to undergo some modifications or processing to transform into a mature mRNA.  Following these modifications a single gene can produce more than one protein.

a. Splicing

The pre-mRNA is comprised of introns and exons. Introns are the regions that do not code for the protein, whereas exons are the regions that code for the protein.In splicing, noncoding regions or introns of the mRNA get removed under the influence of ribonucleoproteins.

Here, the mRNA gets edited, that is, its some of the nucleotides get changed. For instance, a human protein called Apolipoprotein B (APOB), which helps in lipid transportation in the blood, comes in two different forms due to this editing. One form is smaller than the other because an earlier stop signal gets added in mRNA due to editing.

c. 5’ Capping

In this process, a methylated cap is added to the 5′ end or ‘head’ of the mRNA, replacing the triphosphate group.  This cap helps with mRNA recognition by the ribosome during translation, and also protects the mRNA from breaking down.

d. Polyadenylation

At the opposite end of the RNA transcript, that is, to the 3′ end of the RNA chain 30-500 adenines are added, forming the poly A tail. It signals the end of mRNA, and is involved in exporting mRNA from the nucleus.

2) Translation: The Second Step of Protein Synthesis

Translation, the next major step of protein synthesis is the process in which the genetic code in mRNA is read to make the amino acids, which are linked together in a particular order based on the genetic code, forming protein.

Similar to transcription, translation also occurs in three stages: initiation, elongation, and termination.

After the mature mRNA leaves the nucleus, it travels to a ribosome. The 5′ methylated cap of the mRNA, containing the strat codon binds to the small ribosomal subunit of the ribosome consisting rRNA. Next, a tRNA containing anticodons complementary to the start codon on the mRNA attaches to the ribosome.  These mRNA, ribosome, and tRNA together form an initiation complex.The ribosome reads the sequence of codons in mRNA, and tRNA bring amino acids to the ribosome in the proper sequence.

Once the initiation complex is formed, the large ribosomal subunit of ribosome binds to this complex, releasing initiation factors (IFs). The large subunit of the ribosome has three sites for tRNA binding; A site, P site, and E site. The A (amino acid) site is the region, where the complementary anticodons of aminoacyl-tRNA (tRNA with amino acid) pairs up with the mRNA codon. This ensures that correct amino acid is added to the growing polypeptide chain at the P (polypeptide) site. Once this transfer is complete, the tRNA leaves the ribosome at the E (exit) site and returns to the cytoplasm to bind another amino acid. The whole process gets repeated continuously and the polypeptide chain gets elongated. The rRNA binds the newly formed amino acids via peptide bond, forming the polypeptide chains.

The 3′ poly A tail of the mRNA holds a stop codon that signals to end the elongation stage. A specialized protein called release factor gets attached to the tail o mRNA, causing the entire initiation complex along with the polypeptide chain to break down. As a result, all the components are released.

What Happens Next

After translation, the newly formed polypeptide chain undergoes either of the two post-translational modifications discussed below:

• Proteolysis : Here, the proteins get cleaved, that is, their N-terminal, C-terminal, or the internal amino-acid residues are removed from the polypeptide by the action of proteases.
• Protein folding : In this stage, the nascent proteins get folded to achieve the secondary and tertiary structures.

After these modifications, the protein may bind with other polypeptides or with different types of molecules, such as lipids or carbohydrates, forming lipoproteins or glycoproteins, respectively. Many proteins travel to the Golgi apparatus where they are modified according to their role in cell.

Why is Protein Synthesis Important

As we can see, this complex process of protein synthesis leads to the formation of proteins that plays several crucial roles in cells, including formation of structural components of cell, like cell membrane , cell repair, producing hormones, enzymes, and many more.

Why is it Different in Prokaryotes and Eukaryotes

The speed of protein synthesis is different in prokaryotes and eukaryotes. In prokaryotes, the process is faster, as the whole process takes place in the cytoplasm. On the other hand, in eukaryotes it is slower, as the pre- mRNA is first synthesized in the nucleus and after splicing, the mature mRNA comes to the cytoplasm for translation.

Ans.   mRNA carries the coding sequences for protein synthesis from DNA to ribosome. tRNA decodes a specific codon of mRNA and transfers a specific amino acid to the ribosome.

Ans. Three types of RNAs are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA).

Ans. Deoxyribonucleic acid (DNA) provides the master code for protein synthesis.

Ans . The codon AUG, coding for methionine starts protein synthesis.

Ans . The two organelles that are involved in protein synthesis are: nucleus and ribosome.

Ans . Well defined reading frames are critical in protein synthesis, because without a well-defined reading frame, the peptide made from a given sequence could be completely different.

Ans . Yes, protein synthesis requires energy.

Ans . Protein synthesis is the process of producing a functional protein molecule based on the information in the genes. On the contrary, DNA replication produces a replica of an existing DNA molecule.

• Protein Synthesis – Flexbooks.ck12.org
• Translation: DNA to mRNA to Protein – Nature.com
• What is protein synthesis – Proteinsynthesis.org
• Translation: Making Protein Synthesis Possible – Thoughtco.com
• Protein Synthesis in the Cell and the Central Dogma – Study.com

Article was last reviewed on Friday, February 17, 2023

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5.7 Protein Synthesis

Created by: CK-12/Adapted by Christine Miller

The Art of Protein Synthesis

This amazing artwork (Figure 5.7.1) shows a process that takes place in the cells of all living things: the production of proteins. This process is called protein synthesis , and it   actually consists of two processes —  transcription  and translation . In eukaryotic  cells, transcription takes place in the  nucleus . During transcription,  DNA  is used as a template to make a molecule of messenger RNA ( mRNA ). The molecule of mRNA then leaves the nucleus and goes to a  ribosome  in the cytoplasm , where translation occurs. During translation, the genetic code in mRNA is read and used to make a polypeptide. These two processes are summed up by the central dogma of molecular biology:  DNA   → RNA   →   Protein .

Transcription

Transcription  is the first part of the central dogma of molecular biology:  DNA   →   RNA . It is the transfer of genetic instructions in DNA to mRNA. During transcription, a strand of mRNA is made to complement a strand of DNA. You can see how this happens in Figure 5.7.2.

Transcription begins when the enzyme RNA polymerase binds to a region of a gene called the promoter sequence. This signals the DNA to unwind so the enzyme can “read” the bases of DNA.  The two strands of DNA are named based on whether they will be used as a template for RNA or not.  The strand that is used as a template is called the template strand, or can also be called the a ntisense strand.  The sequence of bases on the opposite strand of DNA is called the coding or sense strand.  Once the DNA has opened, and RNA polymerase has attached, the RNA polymerase moves along the DNA, adding RNA nucleotides to the growing mRNA strand.  The template strand of DNA is used as to create mRNA through complementary base pairing. Once the mRNA strand is complete, and it detaches from DNA. The result is  a strand of mRNA that is nearly identical to the coding strand DNA – the only difference being that DNA uses the base thymine, and the mRNA uses uracil in the place of thymine

Processing mRNA

In eukaryotes , the new mRNA is not yet ready for translation. At this stage, it is called pre-mRNA, and it must go through more processing before it leaves the nucleus as mature mRNA. The processing may include splicing, editing, and polyadenylation. These processes modify the mRNA in various ways. Such modifications allow a single gene to be used to make more than one protein.

• Splicing removes introns from mRNA, as shown in Figure 5.7.3. Introns  are regions that do not code for the protein. The remaining mRNA consists only of regions called  exons  that do code for the protein. The ribonucleoproteins in the diagram are small proteins in the nucleus that contain RNA and are needed for the splicing process.
• Editing changes some of the nucleotides in mRNA. For example, a human protein called APOB, which helps transport lipids in the blood, has two different forms because of editing. One form is smaller than the other because editing adds an earlier stop signal in mRNA.
• 5′ Capping  adds a methylated cap to the “head” of the mRNA.  This cap protects the mRNA from breaking down, and helps the ribosomes know where to bind to the mRNA
• Polyadenylation adds a “tail” to the mRNA. The tail consists of a string of As (adenine bases). It signals the end of mRNA. It is also involved in exporting mRNA from the nucleus, and it protects mRNA from enzymes that might break it down.

Translation

Translation  is the second part of the central dogma of molecular biology:  RNA → Protein . It is the process in which the genetic code in mRNA is read to make a protein . Translation is illustrated in Figure 5.7.4. After mRNA leaves the nucleus , it moves to a ribosome , which consists of rRNA and proteins. The ribosome reads the sequence of codons in mRNA, and molecules of tRNA bring amino acids to the ribosome in the correct sequence.

Translation occurs in three stages: Initiation, Elongation and Termination.

Initiation:

After transcription in the nucleus, the mRNA exits through a nuclear pore and enters the cytoplasm.  At the region on the mRNA containing the methylated cap and the start codon, the small and large subunits of the ribosome  bind to the mRNA.  These are then joined by a tRNA which contains the anticodons matching the start codon on the mRNA.  This group of molecues (mRNA, ribosome, tRNA) is called an initiation complex.

Elongation:

tRNA keep bringing amino acids to the growing polypeptide according to complementary base pairing between the codons on the mRNA and the anticodons on the tRNA.  As a tRNA moves into the ribosome, its amino acid is transferred to the growing polypeptide.  Once this transfer is complete, the tRNA leaves the ribosome, the ribosome moves one codon length down the mRNA, and a new tRNA enters with its corresponding amino acid.  This process repeats and the polypeptide grows.

Termination :

At the end of the mRNA coding is a stop codon which will end the elongation stage.  The stop codon doesn’t call for a tRNA, but instead for a type of protein called a release factor, which will cause the entire complex (mRNA, ribosome, tRNA, and polypeptide) to break apart, releasing all of the components.

Watch this video “Protein Synthesis (Updated) with the Amoeba Sisters” to see this process in action:

Protein Synthesis (Updated), Amoeba Sisters, 2018.

What Happens Next?

After a polypeptide chain is synthesized, it may undergo additional processes. For example, it may assume a folded shape due to interactions between its amino acids. It may also bind with other polypeptides or with different types of molecules, such as lipids or carbohydrates . Many proteins travel to the Golgi apparatus within the cytoplasm to be modified for the specific job they will do. 7 Summary

5.7 Summary

• Protein synthesis is the process in which cells make proteins. It occurs in two stages: transcription and translation.
• Transcription is the transfer of genetic instructions in DNA to mRNA in the nucleus. It includes three steps: initiation, elongation, and termination. After the mRNA is processed, it carries the instructions to a ribosome in the cytoplasm.
• Translation occurs at the ribosome, which consists of rRNA and proteins. In translation, the instructions in mRNA are read, and tRNA brings the correct sequence of amino acids to the ribosome. Then, rRNA helps bonds form between the amino acids, producing a polypeptide chain.
• After a polypeptide chain is synthesized, it may undergo additional processing to form the finished protein.

5.7 Review Questions

• Relate protein synthesis and its two major phases to the central dogma of molecular biology.
• Explain how mRNA is processed before it leaves the nucleus.
• What additional processes might a polypeptide chain undergo after it is synthesized?
• Where does transcription take place in eukaryotes?
• Where does translation take place?

5.7 Explore More

Protein Synthesis, Teacher’s Pet, 2014.

Attributions

Figure 5.7.1

How proteins are made by Nicolle Rager, National Science Foundation on Wikimedia Commons is released into the public domain (https://en.wikipedia.org/wiki/Public_domain) .

Figure 5.7.2

Transcription by National Human Genome Research Institute , (reworked and vectorized by Sulai) on Wikimedia Commons is released into the public domain (https://en.wikipedia.org/wiki/Public_domain) .

Figure 5.7.3

Pre mRNA processing by Christine Miller is used under a CC BY-NC-SA 4.0   (https://creativecommons.org/licenses/by-nc-sa/4.0/) license.

Figure 5.7.4

Translation  by CNX OpenStax on Wikimedia Commons is used under a CC BY 4.0 (https://creativecommons.org/licenses/by/4.0) license.

Amoeba Sisters. (2018, January 18) Protein synthesis (Updated). YouTube. https://www.youtube.com/watch?v=oefAI2x2CQM&feature=youtu.be

Parker, N., Schneegurt, M., Thi Tu, A-H., Lister, P., Forster, B.M. (2016, November 1). Microbiology [online]. Figure 11.15 Translation in bacteria begins with the formation of the initiation complex. In Microbiology (Section 11-4). OpenStax. https://openstax.org/books/microbiology/pages/11-4-protein-synthesis-translation

Teacher’s Pet. (2014, December 7). Protein synthesis. YouTube. https://www.youtube.com/watch?v=2zAGAmTkZNY&feature=youtu.be

The process of creating protein molecules.

The process by which DNA is copied (transcribed) to mRNA in order transfer the information needed for protein synthesis.

The process in which mRNA along with transfer RNA (tRNA) and ribosomes work together to produce polypeptides.

Cells which have a nucleus enclosed within membranes, unlike prokaryotes, which have no membrane-bound organelles.

A central organelle containing hereditary material.

Deoxyribonucleic acid - the molecule carrying genetic instructions for the development, functioning, growth and reproduction of all known organisms and many viruses.

A large family of RNA molecules that convey genetic information from DNA to the ribosome, where they specify the amino acid sequence of the protein products of gene expression.

A large complex of RNA and protein which acts as the site of RNA translation, building proteins from amino acids using messenger RNA as a template.

The jellylike material that makes up much of a cell inside the cell membrane, and, in eukaryotic cells, surrounds the nucleus. The organelles of eukaryotic cells, such as mitochondria, the endoplasmic reticulum, and (in green plants) chloroplasts, are contained in the cytoplasm.

A nucleic acid of which many different kinds are now known, including messenger RNA, transfer RNA and ribosomal RNA.

A class of biological molecule consisting of linked monomers of amino acids and which are the most versatile macromolecules in living systems and serve crucial functions in essentially all biological processes.

The addition of a poly(A) tail to a messenger RNA. The poly(A) tail consists of multiple adenosine monophosphates.

A sequence of 3 DNA or RNA nucleotides that corresponds with a specific amino acid or stop signal during protein synthesis.

A small RNA molecule that participates in protein synthesis. Each tRNA molecule has two important areas: an anticodon and a region for attaching a specific amino acid.

Amino acids are organic compounds that combine to form proteins.

A substance that is insoluble in water. Examples include fats, oils and cholesterol. Lipids are made from monomers such as glycerol and fatty acids.

A biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1. Complex carbohydrates are polymers made from monomers of simple carbohydrates, also termed monosaccharides.

A membrane-bound organelle found in eukaryotic cells made up of a series of flattened stacked pouches with the purpose of collecting and dispatching protein and lipid products received from the endoplasmic reticulum (ER). Also referred to as the Golgi complex or the Golgi body.

Human Biology Copyright © 2020 by Christine Miller is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License , except where otherwise noted.

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3.4 Protein Synthesis

Learning objectives.

Main Objective

• Explain the process by which a cell builds proteins using the DNA code

By the end of this section, you will be able to:

• Explain how the genetic code within DNA determines the proteins formed
• Describe the process of transcription
• Explain the process of translation
• Discuss the function of ribosomes

It was mentioned earlier that DNA provides a “blueprint” for the cell structure and physiology. This refers to the fact that DNA contains the information necessary for the cell to build one very important type of molecule: the protein. Most structural components of the cell are made up, at least in part, by proteins and virtually all the functions that a cell carries out are completed with the help of proteins. One of the most important classes of proteins is enzymes, which help speed up necessary biochemical reactions that take place inside the cell. Some of these critical biochemical reactions include building larger molecules from smaller components (such as what occurs during DNA replication or synthesis of microtubules) and breaking down larger molecules into smaller components (such as when harvesting chemical energy from nutrient molecules). Whatever the cellular process may be, it is almost sure to involve proteins. Just as the cell’s genome describes its full complement of DNA, a cell’s proteome is its full complement of proteins. Protein synthesis begins with genes. A gene is a functional segment of DNA that provides the genetic information necessary to build a protein. Each particular gene provides the code necessary to construct a particular protein. Gene expression , which transforms the information coded in a gene to a final gene product, ultimately dictates the structure and function of a cell by determining which proteins are made.

The interpretation of genes works in the following way. Recall that proteins are polymers, or chains, of many amino acid building blocks. The sequence of bases in a gene (that is, its sequence of A, T, C, G nucleotides) translates to an amino acid sequence. A triplet is a section of three DNA bases in a row that codes for a specific amino acid. For example, the DNA triplet CAC (cytosine, adenine, and cytosine) specifies the amino acid valine. Therefore, a gene, which is composed of multiple triplets in a unique sequence, provides the code to build an entire protein, with multiple amino acids in the proper sequence ( Figure 3.4.1 ). The mechanism by which cells turn the DNA code into a protein product is a two-step process, with an RNA molecule as the intermediate.

From DNA to RNA: Transcription

DNA is housed within the nucleus, and protein synthesis takes place in the cytoplasm, thus there must be some sort of intermediate messenger that leaves the nucleus and manages protein synthesis. This intermediate messenger is messenger RNA (mRNA) , (Figure 3.29), a single-stranded nucleic acid that carries a copy of the genetic code for a single gene out of the nucleus and into the cytoplasm where it is used to produce proteins.

There are several different types of RNA, each having different functions in the cell. The structure of RNA is similar to DNA with a few small exceptions. For one thing, unlike DNA, most types of RNA, including mRNA, are single-stranded and contain no complementary strand. Second, the ribose sugar in RNA contains an additional oxygen atom compared with DNA. Finally, instead of the base thymine, RNA contains the base uracil. This means that adenine will always pair up with uracil during the protein synthesis process.

Gene expression begins with the process called transcription , which is the synthesis of a strand of mRNA that is complementary to the gene of interest. This process is called transcription because the mRNA is like a transcript, or copy, of the gene’s DNA code. Transcription begins in a fashion somewhat like DNA replication, in that a region of DNA unwinds and the two strands separate, however, only that small portion of the DNA will be split apart. The triplets within the gene on this section of the DNA molecule are used as the template to transcribe the complementary strand of RNA ( Figure 3.4.2 ). A codon is a three-base sequence of mRNA, so-called because they directly encode amino acids. Like DNA replication, there are three stages to transcription: initiation, elongation, and termination.

In the first of the two stages of making protein from DNA, a gene on the DNA molecule is transcribed into a complementary mRNA molecule.

Stage 1: Initiation. A region at the beginning of the gene called a promoter—a particular sequence of nucleotides—triggers the start of transcription.

Stage 2: Elongation. Transcription starts when RNA polymerase unwinds the DNA segment. One strand, referred to as the coding strand, becomes the template with the genes to be coded. The polymerase then aligns the correct nucleic acid (A, C, G, or U) with its complementary base on the coding strand of DNA. RNA polymerase is an enzyme that adds new nucleotides to a growing strand of RNA. This process builds a strand of mRNA.

Stage 3: Termination. When the polymerase has reached the end of the gene, one of three specific triplets (UAA, UAG, or UGA) codes a “stop” signal, which triggers the enzymes to terminate transcription and release the mRNA transcript.

The transcription process is regulated by a class of proteins called transcription factors , which bind to the gene sequence and either promote or inhibit their transcription.   (move Figure 3.35 here).

Before the mRNA molecule leaves the nucleus and proceeds to protein synthesis, it is modified in a number of ways. For this reason, it is often called a pre-mRNA at this stage. For example, your DNA, and thus complementary mRNA, contains long regions called non-coding regions that do not code for amino acids. Their function is still a mystery, but the process called splicing removes these non-coding regions from the pre-mRNA transcript ( Figure 3.4.3 ). A spliceosome —a structure composed of various proteins and other molecules—attaches to the mRNA and “splices” or cuts out the non-coding regions. The removed segment of the transcript is called an intron . The remaining exons are pasted together. An exon is a segment of RNA that remains after splicing. Interestingly, some introns that are removed from mRNA are not always non-coding. When different coding regions of mRNA are spliced out, different variations of the protein will eventually result, with differences in structure and function. This process results in a much larger variety of possible proteins and protein functions. When the mRNA transcript is ready, it travels out of the nucleus and into the cytoplasm.

External Website

This video will show you the important enzymes and biomolecules involved in the process of transcription, the process of making an mRNA molecule from DNA.

From RNA to Protein: Translation

Like translating a book from one language into another, the codons on a strand of mRNA must be translated into the amino acid alphabet of proteins. Translation is the process of synthesizing a chain of amino acids called a polypeptide. Translation requires two major aids: first, a “translator,” the molecule that will conduct the translation, and second, a substrate on which the mRNA strand is translated into a new protein, like the translator’s “desk.” Both of these requirements are fulfilled by other types of RNA. The substrate on which translation takes place is the ribosome.

Remember that many of a cell’s ribosomes are found associated with the rough ER, and carry out the synthesis of proteins destined for the Golgi apparatus. Ribosomal RNA (rRNA) is a type of RNA that, together with proteins, composes the structure of the ribosome. Ribosomes exist in the cytoplasm as two distinct components, a small and a large subunit. When an mRNA molecule is ready to be translated, the two subunits come together and attach to the mRNA. The ribosome provides a substrate for translation, bringing together and aligning the mRNA molecule with the molecular “translators” that must decipher its code.

The other major requirement for protein synthesis is the translator molecules that physically “read” the mRNA codons. Transfer RNA (tRNA) is a type of RNA that ferries the appropriate corresponding amino acids to the ribosome, and attaches each new amino acid to the last, building the polypeptide chain one-by-one. Thus tRNA transfers specific amino acids from the cytoplasm to a growing polypeptide. The tRNA molecules must be able to recognize the codons on mRNA and match them with the correct amino acid. The tRNA is modified for this function. On one end of its structure is a binding site for a specific amino acid. On the other end is a base sequence that matches the codon specifying its particular amino acid. This sequence of three bases on the tRNA molecule is called an anticodon . For example, a tRNA responsible for shuttling the amino acid glycine contains a binding site for glycine on one end. On the other end it contains an anticodon that complements the glycine codon (GGA is a codon for glycine, and so the tRNAs anticodon would read CCU). Equipped with its particular cargo and matching anticodon, a tRNA molecule can read its recognized mRNA codon and bring the corresponding amino acid to the growing chain ( Figure 3.4.4 ).

Much like the processes of DNA replication and transcription, translation consists of three main stages: initiation, elongation, and termination. Initiation takes place with the binding of a ribosome to an mRNA transcript. The elongation stage involves the recognition of a tRNA anticodon with the next mRNA codon in the sequence. Once the anticodon and codon sequences are bound (remember, they are complementary base pairs), the tRNA presents its amino acid cargo and the growing polypeptide strand is attached to this next amino acid. This attachment takes place with the assistance of various enzymes and requires energy. The tRNA molecule then releases the mRNA strand, the mRNA strand shifts one codon over in the ribosome, and the next appropriate tRNA arrives with its matching anticodon. This process continues until the final codon on the mRNA is reached which provides a “stop” message that signals termination of translation and triggers the release of the complete, newly synthesized protein. Thus, a gene within the DNA molecule is transcribed into mRNA, which is then translated into a protein product ( Figure 3.4.5 ).

This video will show you the important enzymes and biomolecules involved in the process of translation, which uses mRNA to code for a protein.

Commonly, an mRNA transcription will be translated simultaneously by several adjacent ribosomes. This increases the efficiency of protein synthesis. A single ribosome might translate an mRNA molecule in approximately one minute; so multiple ribosomes aboard a single transcript could produce multiple times the number of the same protein in the same minute. A polyribosome is a string of ribosomes translating a single mRNA strand.

Watch this  video  to learn about ribosomes. The ribosome binds to the mRNA molecule to start translation of its code into a protein. What happens to the small and large ribosomal subunits at the end of translation?

Chapter Review

DNA stores the information necessary for instructing the cell to perform all of its functions. Cells use the genetic code stored within DNA to build proteins, which ultimately determines the structure and function of the cell. This genetic code lies in the particular sequence of nucleotides that make up each gene along the DNA molecule. To “read” this code, the cell must perform two sequential steps. In the first step, transcription, the DNA code is converted into a RNA code. A molecule of messenger RNA that is complementary to a specific gene is synthesized in a process similar to DNA replication. The molecule of mRNA provides the code to synthesize a protein. In the process of translation, the mRNA attaches to a ribosome. Next, tRNA molecules shuttle the appropriate amino acids to the ribosome, one-by-one, coded by sequential triplet codons on the mRNA, until the protein is fully synthesized. When completed, the mRNA detaches from the ribosome, and the protein is released. Typically, multiple ribosomes attach to a single mRNA molecule at once such that multiple proteins can be manufactured from the mRNA concurrently.

Review Questions

Critical thinking questions.

Briefly explain the similarities between transcription and DNA replication.

Transcription and DNA replication both involve the synthesis of nucleic acids. These processes share many common features—particularly, the similar processes of initiation, elongation, and termination. In both cases the DNA molecule must be untwisted and separated, and the coding (i.e., sense) strand will be used as a template. Also, polymerases serve to add nucleotides to the growing DNA or mRNA strand. Both processes are signaled to terminate when completed.

Contrast transcription and translation. Name at least three differences between the two processes.

Transcription is really a “copy” process and translation is really an “interpretation” process, because transcription involves copying the DNA message into a very similar RNA message whereas translation involves converting the RNA message into the very different amino acid message. The two processes also differ in their location: transcription occurs in the nucleus and translation in the cytoplasm. The mechanisms by which the two processes are performed are also completely different: transcription utilizes polymerase enzymes to build mRNA whereas translation utilizes different kinds of RNA to build protein.

This work, Anatomy & Physiology, is adapted from Anatomy & Physiology by OpenStax , licensed under CC BY . This edition, with revised content and artwork, is licensed under CC BY-SA except where otherwise noted.

Images, from Anatomy & Physiology by OpenStax , are licensed under CC BY except where otherwise noted.

Access the original for free at https://openstax.org/books/anatomy-and-physiology/pages/1-introduction .

Anatomy & Physiology Copyright © 2019 by Lindsay M. Biga, Staci Bronson, Sierra Dawson, Amy Harwell, Robin Hopkins, Joel Kaufmann, Mike LeMaster, Philip Matern, Katie Morrison-Graham, Kristen Oja, Devon Quick, Jon Runyeon, OSU OERU, and OpenStax is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License , except where otherwise noted.

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Cooper GM. The Cell: A Molecular Approach. 2nd edition. Sunderland (MA): Sinauer Associates; 2000.

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The Cell: A Molecular Approach. 2nd edition.

Chapter 7 protein synthesis, processing, and regulation.

Transcription and RNA processing are followed by translation , the synthesis of proteins as directed by mRNA templates. Proteins are the active players in most cell processes, implementing the myriad tasks that are directed by the information encoded in genomic DNA . Protein synthesis is thus the final stage of gene expression. However, the translation of mRNA is only the first step in the formation of a functional protein. The polypeptide chain must then fold into the appropriate three-dimensional conformation and, frequently, undergo various processing steps before being converted to its active form. These processing steps, particularly in eukaryotes, are intimately related to the sorting and transport of different proteins to their appropriate destinations within the cell.

Although the expression of most genes is regulated primarily at the level of transcription (see Chapter 6), gene expression can also be controlled at the level of translation , and this control is an important element of gene regulation in both prokaryotic and eukaryotic cells . Of even broader significance, however, are the mechanisms that control the activities of proteins within cells. Once synthesized, most proteins can be regulated in response to extracellular signals by either covalent modifications or by association with other molecules. In addition, the levels of proteins within cells can be controlled by differential rates of protein degradation. These multiple controls of both the amounts and activities of intracellular proteins ultimately regulate all aspects of cell behavior.

• Translation of mRNA
• Protein Folding and Processing
• Regulation of Protein Function
• Protein Degradation
• References and Further Reading
• Cite this Page Cooper GM. The Cell: A Molecular Approach. 2nd edition. Sunderland (MA): Sinauer Associates; 2000. Chapter 7, Protein Synthesis, Processing, and Regulation.
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Microbe Notes

Protein Synthesis: Enzymes, Sites, Steps, Inhibitors

Protein Synthesis is a process of synthesizing proteins in a chain of amino acids known as polypeptides. It is the second part of the central dogma in genetics.

• It takes place in the ribosomes found in the cytosol or those attached to the rough endoplasmic reticulum.
• The functions of the ribosome are to read the sequence of the codons in mRNA and the tRNA molecules that transfer or transport or bring the amino acids to the ribosomes in the correct sequence. However, other molecules are also involved in the process of translation such as various enzymatic factors.
• The translation process involves reading the genetic code in mRNA to make proteins.
• The entire translation process can be summarized into three phases: Initiation, elongation, and termination.

Figure: Central Dogma.

Table of Contents

Interesting Science Videos

Protein Synthesis Machinery

The translation process is aided by two major factors: A translator – this is the molecule that conducts the translation; substrate – this is where the mRNA is translated into a new protein (translator desk). The translation process is guided by machinery composed of:

• Ribosomes are made of ribosomal RNA (rRNA) and proteins, and therefore they are also named ribozymes because the rRNA has enzymatic activity. the rRNA has the peptidyl transferase activity that bonds the amino acids.
• The ribosomes have two subunits of rRNA and proteins, a large subunit with three active sites (E, P, A) which are critical for the catalytic activity of ribosomes.

Transfer RNA (tRNA)

• Each tRNA has an anticodon for the amino acid codon it carries which are complementary to each other. For example; Lysine is coded by AAG, and therefore the anticodon that will be carried by tRNA will be UUC, therefore when the codon AAG appears, an anticodon UUC of tRNA will bind to it temporarily.
• When tRNA is bound to mRNA, the tRNA then releases its amino acid. rRNA then helps to form bonds between the amino acids as they are transported to the ribosomes one by one, thus creating a polypeptide chain. The polypeptide chain keeps growing until it reaches a stop codon.

Protein Synthesis enzymes and functions

• Peptidyl transferase is the main enzyme used in Translation. It is found in the ribosomes with an enzymatic activity that catalyzes the formation of a covalent peptide bond between the adjacent amino acids.
• The enzyme’s activity is to form peptide bonds between adjacent amino acids using tRNAs during translation.
• The enzyme’s activity uses two substrates of which one has the growing peptide chain and the other bears the amino acid that is added to the chain.
• It is located in the large subunit of the ribosomes and therefore, the primary function of peptidyl transferase is to catalyze the addition of amino acid residues allowing the polypeptide chain to grow.
• The peptidyl transferase enzyme is entirely made up of RNA and its mechanism is mediated by ribosomal RNA (rRNA), which is a ribozyme, made up of ribonucleotides.
• In prokaryotes, the 23S subunit contains the peptidyl transferase between the A-site and the O-site of tRNA while in eukaryotes, it is found in the 28S subunit.

Overview of the Protein Synthesis

• The ribosomal translation is initiated when the ribosomes recognize the starting point of mRNA, where it binds a molecule of tRNA that bears a single amino acid.
• In prokaryotes, the initial amino acid in N-formylmethionine. during elongation, the second amino acid is linked to the first one.
• The ribosome then shifts its position on the mRNA and repeats the elongation cycle.
• When the elongation process reaches the stop codon, the amino acid chain folds spontaneously to form a protein.
• The ribosomes then split into two subunits, but later rejoin before another mRNA is translated.
• Protein synthesis is facilitated by several catalytic proteins which include initiation, elongation, termination factors, and guanosine triphosphates (GTP).
• GTP is a molecule that releases energy when converted into guanosine diphosphate (GDP).

Protein Synthesis Steps /Process in Details

Translation initiation.

• Protein synthesis initiation is triggered by the presence of several initiation factors IF1, IF2, and IF3, including mRNA, ribosomes, tRNA.
• The small subunit binds to the upstream on the 5′ end at the start of mRNA. The ribosome scans the mRNA in the 5′ to 3′ direction until it encounters the start codon (AUG or GUG or UUG). When either of these start codons is present, it is recognized by the initiator fMet-tRNA (N-formylMet-tRNA). This initiator factor carries the methionine (Met) which binds to the P site on the ribosome.
• This synthesizes the first amino acid polypeptide known as N-formylmethionine. The initiator fMet-tRNA has a normal methionine anticodon therefore it inserts the N-formylmethionine. This means that methionine is the first amino acid that is added and appears in the chain.
• Generally, there are three steps in the initiation process of translation;
• Initiation of the binding of mRNA to the small ribosome subunit (the 30S), stimulating the initiator factor IF3. this dissociates the ribosomal subunits into two.
• The initiator factor IF2 then binds to the Guanine-triphosphate (GTP) and to the initiator fMet-tRNA to the P-site of the ribosomes.
• A ribosomal protein splits the GTP that is bound to IF2 thus helping in driving the assembly of the two ribosomal subunits. The IF3 and IF2 are released.

Translation Elongation

• The elongation of protein synthesis is aided by three protein factors i.e EF-Tu, EF-Ts , and EF-G .
• The ribosomal function is known to shift one codon at a time, catalyzing the processes that take place in its three sites.
• For every step, a charged tRNA enters the ribosomal complex and inserts the polypeptides that become one amino acid longer, while an uncharged tRNA departs. In prokaryotes, an amino acid is added at least every 0.05 seconds, which means that about 200 polypeptide amino acids are translated in 10 seconds.
• The bond created between each amino acid is derived from the Guanosine Triphosphate (GTP), which is similar to Adenosine Triphosphate (ATP).
• The three sites (A, P, E) all participate in the translation process, and the ribosome itself interacts with all the RNA types involved in translation.
• Therefore, three distinct steps are involved in translation, and these are;
• The mediation of elongation Factor-Tu (EF-Tu) in the entry of amino-acyl-tRNAs to the A site. This entails the binding of EF-Tu to GTP, which activates the EF-Tu-GTP complex to bind to tRNA. The GTP then hydrolyses to GDP releasing an energy-giving phosphate molecule, thus driving the binding of aminoacyl-tRNA to the A site. At this point the EF-Tu is released, leaving the tRNA in the A-site.
• Elongation factor EF-Ts then mediates the releasing of EF-Tu-GDP complex from the ribosomes and the formation of the EF-Tu-GTP.
• During this translocation process, the polypeptide chain on the peptidyl-tRNA is transferred to the aminoacyl-tRNA on the A-site during a reaction that is catalyzed by a peptidyl transferase. The ribosomes then move one codon further along the mRNA in the 5′ to 3′ direction mediated by the elongation factor EF-G. This step draws its energy from the splitting of GTP to GDP. Uncharged tRNA is released from the P-site, transferring newly formed peptidyl-tRNA from the A-site to the P-site.

Translation Termination

• Termination of the translation process is triggered by an encounter of any of the three stop codons (UAA, UAG, UGA). These triplet stop codons, however, are not recognized by the tRNA but by protein factors known as the release factors, (RF1 and RF2) found in the ribosomes.
• The RF1 recognizes the triplet UAA and UAG while RF2 recognizes UAA and UGA. A third factor also assists in catalyzing the termination process and it’s known as Release factor 3 (RF3).
• When the peptidyl-tRNA from the elongation step arrives at the P site, the release factor of the stop codon binds to the A site. These releases the polypeptide from the P site allowing the ribosomes to dissociate into two subunits by the energy derived from GTP, leaving the mRNA.
• After many ribosomes have completed the translation process, the mRNA is degraded allowing its nucleotides to be reused in other transcription reactions.

Protein Synthesis Video Animation (Amoeba Sisters)

Eukaryotes Protein Synthesis vs. Prokaryotes Protein Synthesis

Protein Synthesis Inhibitors

Antimicrobial agents are used as protein synthesis inhibitors which include:

• This is an antibiotic that is an analog of the terminal aminoacyl-adenosine part of aminoacyl-tRNA. This antibiotic inhibits protein synthesis by releasing prokaryotic polypeptides chains before they are completely synthesized. Its mechanism is achieved by joining its amino group to the carbonyl group of the growing polypeptide chain on the A-site forming an adduct that dissociates from the ribosome.
• Puromycin also contains an α-amino group similar to that on the aminoacyl-tRNA, which forms a covalently bound peptide bond with the carboxyl group of the growing peptide with puromycin residues, thus contributing to the dissociation of the ribosomes.
• This is a trisaccharide that has an effect on the binding activity of formyl methionyl-tRNA to ribosomes. This prevents the correct initiation of protein synthesis.
• Aminoglycoside antibiotics such as neomycin, kanamycin, and gentamycin which interfere with the decoding site in the 16s rRNA of the small subunit.
• Chloramphenicol inhibits the activity of peptidyl transferase.
• Erythromycin blocks translocation by binding to the 50S subunit
• Cycloheximide is used to block peptidyl transferase in eukaryotic ribosomes and it is used as a laboratory tool for blocking protein synthesis in eukaryotic cells.
• Diphtheria toxin has an A fragment that catalyzes the transfer of a single side chain of EF2 which blocks the translocation of the growing polypeptide chain.

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Faith Mokobi

1 thought on “Protein Synthesis: Enzymes, Sites, Steps, Inhibitors”

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Protein Synthesis

mRNA transcript for translation

If you have jumped straight to this page, you may wish to look at the previous tutorial about DNA , which gives background information on protein synthesis.

As mentioned, a string of  nucleotides  represent the genetic information that makes us unique and the blueprint of who and what we are, and how we operate. Part of this genetic information is devoted to the synthesis of  proteins , which are essential to our body and used in a variety of ways. Proteins are created from templates of information in our DNA, illustrated below:

The X marked nucleotides are an example of a DNA sequence that would be used to code for a particular protein. Every DNA molecule consists of two strands, only one of which is the coding strand containing the information for protein sequences. The complementary strand is the template strand, and it is this strand that the RNA nucleotides line up on to make a copy of the DNA coding strand.

The sequence of these nucleotides is used to create amino acids , which are linked together to make a protein.

In eukaryotes, most genetic information is found in the nucleus, though protein synthesis actually occurs in ribosomes  found in the  cytoplasm, either as free ribosomes or on the rough endoplasmic reticulum.  If protein is to be synthesized, then the genetic information in the  nucleus  must be transferred to these ribosomes. This is done by  mRNA  (messenger ribonucleic acid). It is very similar to DNA, but fundamentally differs in two ways

• The base thymine in DNA is replaced by the base uracil in mRNA.
• The sugar deoxyribose in DNA is replaced by the sugar ribose in mRNA.

At the beginning of protein synthesis, just like DNA replication, the double helix structure of DNA uncoils in order for mRNA to replicate the genetic sequence responsible for the coding of a particular protein.

In the beginning, the DNA has uncoiled, allowing the enzyme RNA polymerase to move in and transcribe (copy) the genetic information into mRNA. If the coding strand of DNA looks like this: G-G-C-A-T-T, then the template strand would look like this: C C G T T A and the mRNA would look like this G G C A U-U (remembering that uracil replaces thymine).

With the genetic information responsible for creating substances now available on the mRNA strand, the mRNA moves out of the nucleus and away from the DNA towards the ribosomes.

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Biology Wise

A Short Explanation of the Fascinating Process of Protein Synthesis

Protein synthesis refers to the construction of proteins by the living cells. Comprising two primary parts (transcription and translation), the process of protein synthesis involves ribonucleic acids (RNA), deoxyribonucleic acid (DNA), enzymes, and ribosomes.

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Proteins are important organic compounds present in living organisms. They are essential in almost all cell functions. Specific proteins are involved with particular functions. Proteins are made up of long chains of amino acids, which are either arranged in a linear pattern, or folded to form a complex structure.

Based on the structural complexity, structure of proteins is classified into four types – primary, secondary, tertiary, and quaternary. Also, the types of amino acids play a crucial role in determining the expression of genes in this process.

Protein synthesis is a biological procedure performed by living cells to manufacture proteins in a step-by-step manner. Many times, it is used to denote translation, which otherwise is a primary part in the protein synthesis process. When studied in detail, the synthesis process is very complex. The process itself begins with production of different amino acids, out of which some are derived from food sources.

Explanation

Protein synthesis comprises two major parts – transcription and translation. The process involves ribonucleic acid (RNA), deoxyribonucleic acid (DNA), and a set of enzymes. All types of ribonucleic acids, namely messenger ribonucleic acid (mRNA), ribosomal ribonucleic acid (rRNA), and transfer ribonucleic acid (tRNA) are required for protein synthesis.

Transcription

It is the first part in the process of protein synthesis. It takes place in the cell nucleus, where deoxyribonucleic acid (DNA) is housed in the chromosomes. As we all know, DNA is a double helix structure. From two parallel strands, one acts as a template to produce mRNA. As an initiation step of transcription, RNA polymerase binds itself to a particular site (promoter region) in one of the DNA strands that will act as a template.

Following its attachment to a DNA template strand, the polymerase enzyme synthesizes a mRNA polymer under the direction of the template DNA. The mRNA strand continues to elongate until the polymerase reaches a ‘terminator region’ in the template.

Hence, the transcription part encompasses three steps – initiation, elongation, and termination. The newly transcribed mRNA is released by the polymerase enzyme, which then migrates to the cytoplasm to complete the process of protein synthesis.

Translation

It is the second part in the process of synthesis of proteins. Contrary to transcription that occurs in the nucleus, translation takes place in the cell cytoplasm. This part is initiated as soon as the transcribed mRNA enters the cytoplasm.

The ribosomes present in the cytoplasm immediately attach to the mRNA at a specific site, called the start codon. An amino acyl tRNA also binds at the mRNA strand. This phase is called initiation.

As the ribosomes move along the mRNA strand, the amino acyl tRNA brings amino acid molecules, one by one. This particular stage is called elongation. At the termination phase, the ribosomes read the last codon of the mRNA strand. This ends the translation part, and the polypeptide chain is released.

In this part, the ribosomes and tRNA get attached to the mRNA, which reads the coded information present in the strand. Accordingly, protein synthesis of a specific amino acid sequence takes place.

Overall, the process of protein synthesis involves transcription of DNA to mRNA, which is then translated into proteins. This process requires proper coordination of RNA, DNA, enzymes, and ribosomes. The stepwise procedure of protein synthesis is also known as ‘central dogma’ in molecular biology.

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3.4 Protein Synthesis

Learning objectives.

By the end of this section, you will be able to:

• Explain how the genetic code stored within DNA determines the protein that will form
• Describe the process of transcription
• Describe the process of translation
• Discuss the function of ribosomes

It was mentioned earlier that DNA provides a “blueprint” for the cell structure and physiology. This refers to the fact that DNA contains the information necessary for the cell to build one very important type of molecule: the protein. Most structural components of the cell are made up, at least in part, by proteins and virtually all the functions that a cell carries out are completed with the help of proteins. One of the most important classes of proteins is enzymes, which help speed up necessary biochemical reactions that take place inside the cell. Some of these critical biochemical reactions include building larger molecules from smaller components (such as occurs during DNA replication or synthesis of microtubules) and breaking down larger molecules into smaller components (such as when harvesting chemical energy from nutrient molecules). Whatever the cellular process may be, it is almost sure to involve proteins. Just as the cell’s genome describes its full complement of DNA, a cell’s proteome is its full complement of proteins. Protein synthesis begins with genes. A gene is a functional segment of DNA that provides the genetic information necessary to build a protein. Each particular gene provides the code necessary to construct a particular protein. Gene expression , which transforms the information coded in a gene to a final gene product, ultimately dictates the structure and function of a cell by determining which proteins are made.

The interpretation of genes works in the following way. Recall that proteins are polymers, or chains, of many amino acid building blocks. The sequence of bases in a gene (that is, its sequence of A, T, C, G nucleotides) translates to an amino acid sequence. A triplet is a section of three DNA bases in a row that codes for a specific amino acid. Similar to the way in which the three-letter code d-o-g signals the image of a dog, the three-letter DNA base code signals the use of a particular amino acid. For example, the DNA triplet CAC (cytosine, adenine, and cytosine) specifies the amino acid valine. Therefore, a gene, which is composed of multiple triplets in a unique sequence, provides the code to build an entire protein, with multiple amino acids in the proper sequence ( Figure 3.25 ). The mechanism by which cells turn the DNA code into a protein product is a two-step process, with an RNA molecule as the intermediate.

From DNA to RNA: Transcription

DNA is housed within the nucleus, and protein synthesis takes place in the cytoplasm, thus there must be some sort of intermediate messenger that leaves the nucleus and manages protein synthesis. This intermediate messenger is messenger RNA (mRNA) , a single-stranded nucleic acid that carries a copy of the genetic code for a single gene out of the nucleus and into the cytoplasm where it is used to produce proteins.

There are several different types of RNA, each having different functions in the cell. The structure of RNA is similar to DNA with a few small exceptions. For one thing, unlike DNA, most types of RNA, including mRNA, are single-stranded and contain no complementary strand. Second, the ribose sugar in RNA contains an additional oxygen atom compared with DNA. Finally, instead of the base thymine, RNA contains the base uracil. This means that adenine will always pair up with uracil during the protein synthesis process.

Gene expression begins with the process called transcription , which is the synthesis of a strand of mRNA that is complementary to the gene of interest. This process is called transcription because the mRNA is like a transcript, or copy, of the gene’s DNA code. Transcription begins in a fashion somewhat like DNA replication, in that a region of DNA unwinds and the two strands separate, however, only that small portion of the DNA will be split apart. The triplets within the gene on this section of the DNA molecule are used as the template to transcribe the complementary strand of RNA ( Figure 3.26 ). A codon is a three-base sequence of mRNA, so-called because they directly encode amino acids. Like DNA replication, there are three stages to transcription: initiation, elongation, and termination.

Stage 1: Initiation. A region at the beginning of the gene called a promoter —a particular sequence of nucleotides—triggers the start of transcription.

Stage 2: Elongation. Transcription starts when RNA polymerase unwinds the DNA segment. One strand, referred to as the coding strand, becomes the template with the genes to be coded. The polymerase then aligns the correct nucleic acid (A, C, G, or U) with its complementary base on the coding strand of DNA. RNA polymerase is an enzyme that adds new nucleotides to a growing strand of RNA. This process builds a strand of mRNA.

Stage 3: Termination. At the end of the gene, a sequence of nucleotides called the terminator sequence causes the new RNA to fold up on itself. This fold causes the RNA to separate from the gene and from RNA polymerase, ending transcription.

Before the mRNA molecule leaves the nucleus and proceeds to protein synthesis, it is modified in a number of ways. For this reason, it is often called a pre-mRNA at this stage. For example, your DNA, and thus complementary mRNA, contains long regions called non-coding regions that do not code for amino acids. Their function is still a mystery, but the process called splicing removes these non-coding regions from the pre-mRNA transcript ( Figure 3.27 ). A spliceosome —a structure composed of various proteins and other molecules—attaches to the mRNA and “splices” or cuts out the non-coding regions. The removed segment of the transcript is called an intron . The remaining exons are pasted together. An exon is a segment of RNA that remains after splicing. Interestingly, some introns that are removed from mRNA are not always non-coding. When different coding regions of mRNA are spliced out, different variations of the protein will eventually result, with differences in structure and function. This process results in a much larger variety of possible proteins and protein functions. When the mRNA transcript is ready, it travels out of the nucleus and into the cytoplasm.

From RNA to Protein: Translation

Like translating a book from one language into another, the codons on a strand of mRNA must be translated into the amino acid alphabet of proteins. Translation is the process of synthesizing a chain of amino acids called a polypeptide . Translation requires two major aids: first, a “translator,” the molecule that will conduct the translation, and second, a substrate on which the mRNA strand is translated into a new protein, like the translator’s “desk.” Both of these requirements are fulfilled by other types of RNA. The substrate on which translation takes place is the ribosome.

Remember that many of a cell’s ribosomes are found associated with the rough ER, and carry out the synthesis of proteins destined for the Golgi apparatus. Ribosomal RNA (rRNA) is a type of RNA that, together with proteins, composes the structure of the ribosome. Ribosomes exist in the cytoplasm as two distinct components, a small and a large subunit. When an mRNA molecule is ready to be translated, the two subunits come together and attach to the mRNA. The ribosome provides a substrate for translation, bringing together and aligning the mRNA molecule with the molecular “translators” that must decipher its code.

The other major requirement for protein synthesis is the translator molecules that physically “read” the mRNA codons. Transfer RNA (tRNA) is a type of RNA that ferries the appropriate corresponding amino acids to the ribosome, and attaches each new amino acid to the last, building the polypeptide chain one-by-one. Thus tRNA transfers specific amino acids from the cytoplasm to a growing polypeptide. The tRNA molecules must be able to recognize the codons on mRNA and match them with the correct amino acid. The tRNA is modified for this function. On one end of its structure is a binding site for a specific amino acid. On the other end is a base sequence that matches the codon specifying its particular amino acid. This sequence of three bases on the tRNA molecule is called an anticodon . For example, a tRNA responsible for shuttling the amino acid glycine contains a binding site for glycine on one end. On the other end it contains an anticodon that complements the glycine codon (GGA is a codon for glycine, and so the tRNAs anticodon would read CCU). Equipped with its particular cargo and matching anticodon, a tRNA molecule can read its recognized mRNA codon and bring the corresponding amino acid to the growing chain ( Figure 3.28 ).

Much like the processes of DNA replication and transcription, translation consists of three main stages: initiation, elongation, and termination. Initiation takes place with the binding of a ribosome to an mRNA transcript. The elongation stage involves the recognition of a tRNA anticodon with the next mRNA codon in the sequence. Once the anticodon and codon sequences are bound (remember, they are complementary base pairs), the tRNA presents its amino acid cargo and the growing polypeptide strand is attached to this next amino acid. This attachment takes place with the assistance of various enzymes and requires energy. The tRNA molecule then releases the mRNA strand, the mRNA strand shifts one codon over in the ribosome, and the next appropriate tRNA arrives with its matching anticodon. This process continues until the final codon on the mRNA is reached which provides a “stop” message that signals termination of translation and triggers the release of the complete, newly synthesized protein. Thus, a gene within the DNA molecule is transcribed into mRNA, which is then translated into a protein product ( Figure 3.29 ).

Commonly, an mRNA transcription will be translated simultaneously by several adjacent ribosomes. This increases the efficiency of protein synthesis. A single ribosome might translate an mRNA molecule in approximately one minute; so multiple ribosomes aboard a single transcript could produce multiple times the number of the same protein in the same minute. A polyribosome is a string of ribosomes translating a single mRNA strand.

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Watch this video to learn about ribosomes. The ribosome binds to the mRNA molecule to start translation of its code into a protein. What happens to the small and large ribosomal subunits at the end of translation?

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The Steps of Protein Synthesis

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Protein synthesis is a vital process that takes place within cells and is an essential mechanism for determining cell structure and function. The processes consist of two steps, transcription and translation.

Protein Synthesis. Image Credit: Soleil Nordic/Shutterstock.com

The first step involves synthesizing messenger RNA (mRNA), which then leaves the nucleus and travels into the cytoplasm where it attaches to a ribosome. At this point, the second step of translation begins where the genetic code of the mRNA molecule is read and used to create a specific protein molecule. Below, we discuss these two steps in detail.

What is Step 1 of Protein Synthesis?

The first stage of transcription involves the transfer of genetic information from DNA into mRNA. The purpose of this stage is to take the information stored in the DNA strand and copy it so that it can be used to create a particular protein molecule. During the phase of transcription, a strand of mRNA is synthesized to complement a specific segment of DNA. This happens in three steps.

First is the step of initiation, which represents the beginning of the transcription process. Here, the enzyme RNA polymerase locates and binds to an area of the gene known are the ‘promoter’. Once the binding has occurred, this signals the DNA strands to begin unwinding, allowing the enzyme RNA polymerase to read the bases of one of its strands. Once complete, the enzyme RNA polymerase can then synthesize a strand of mRNA composed of the same sequence bases.

Next, the step of elongation begins, where nucleotides are added to the strand of mRNA. Finally, once this step is complete, the final step of termination is initiated. Termination is the end of transcription, where the synthesis of the mRNA strand is completed and detaches itself from the DNA.

In humans and other eukaryotes, the newly created strand of mRNA must be processed before it can continue to the second step of protein synthesis, translation. Before processing, the new mRNA is known as pre-mRNA and before leaving the nucleus as mature mRNA must go through a final stage of processing. Often, this involves steps of splicing, editing, and polyadenylation. During these steps, the pre-mRNA molecule is modified, allowing one single gene to be used to create multiple proteins. Below we look at these steps in further detail.

Splicing relies on ribonucleoproteins found in the nucleus and involves the removal of regions go the genetic code, known as introns, from the pre-mRNA. This leaves the pre-mRNA with only protein-coding regions, known as exons.

The second step of processing is the editing phase. This is where changes are made to some of the pre-mRNA’s nucleotides. This editing allows for different versions of a single protein molecule to exist, such as the human protein APOB, which has two forms as a result of editing and works in the body to transport lipids in the blood.

The final step of processing is polyadenylation. This is where a tail of adenine bases is added to the strand of mRNA. The addition of this ‘tail’ signals the end of mRNA and also protects it from enzymes that may try to degrade it once it is exported from the nucleus.

What is the 2nd Step of Protein Synthesis? 

Translation is the second step of protein synthesis. Once transcription and the following processing are complete, translation is initiated. This is where the newly created mRNA’s genetic code is read and used to produce protein molecules. Once mRNA leaves the nucleus it travels to a ribosome. Here, the ribosome reads the chain of codons in the strand of mRNA, and then tRNA transports the corresponding amino acids to the ribosome in the exact sequence.

Each molecule of tRNA has an anticodon to the specific amino acid it carries. Each anticodon has a complementary codon for the specific amino acid. This enables tRNA to transport the correct amino acids in the right order as coded on the strand of mRNA. Once the tRNA arrives at the mRNA with the correct amino acid it temporarily binds to it and gives up its amino acid which bonds to the previously added amino acid in the polypeptide chain. This chain continues to grow until a stop codon is presented.

Summary of the Steps of Protein Synthesis

Protein synthesis is an essential process that happens regularly within cells. The process is used to create new proteins that are used for various vital functions in the body. The process involves two stages of transcription and translation, with the need for processing in-between the two stages.

First, transcription transfers the genetic information from DNA to mRNA via initiation, elongation, and termination. Following this, the newly created strand of mRNA leaves the nucleus and attaches to a ribosome within the cytoplasm. This is where translation initiates. During this stage the genetic data is read, causing tRNA to transport the correct sequence of amino acids to the ribosome, creating a polypeptide chain. Finally, the polypeptide chain may go through the final processing to produce the finished protein molecule.

• Dobson, C., 2003. Protein folding and misfolding. Nature , 426(6968), pp.884-890. https://www.nature.com/articles/nature02261
• Rötig, A., 2011. Human diseases with impaired mitochondrial protein synthesis. Biochimica et Biophysica Acta (BBA) - Bioenergetics , 1807(9), pp.1198-1205. https://www.sciencedirect.com/science/article/pii/S0005272811001526
• Vanzi, F., 2003. Protein synthesis by single ribosomes. RNA , 9(10), pp.1174-1179. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1370481/

Further Reading

• All Proteomics Content
• Progesterone induces sperm release from oviductal epithelial cells by modifying sperm proteomics
• Discovering Misfolded Proteins using Fluorescent Probes
• A Beginners Guide to Plasma Proteomics
• Eliminating American Foulbrood using Endolysins

Last Updated: Jun 28, 2022

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Can You ‘Optimize’ Muscle Protein Synthesis to Gain More Muscle? Experts Weigh In

Your body is a pro at turning the protein you eat into muscle mass—and you can help it along with these tips.

By Sarah Klein • 3 July 2024

How Muscle Protein Synthesis Works

How do exercise and diet affect muscle protein synthesis, can you ‘optimize’ muscle protein synthesis to gain more muscle, the takeaway.

Picture your muscles like a beautiful brick building: Each brick in the walls fits together just so—just like different amino acids (the building blocks of protein) combine to build muscle. When you exercise, you damage some of the brickwork, but your body repairs the damage and builds the wall back stronger. It’s a quintessential image most exercisers have learned about building muscle and strength over time.

But did you know the name for this process is muscle protein synthesis and that it’s constantly running in the background, no matter what you’re up to? Keep reading for all the fascinating details about muscle protein synthesis, plus a few strategic diet and exercise tips to optimize the process.

Let’s unpack muscle protein synthesis, or MPS, a bit further. Plain and simple: It’s how your muscles turn the protein you eat into new muscle , says David Church , PhD, an assistant professor at the Donald W. Reynolds Institute on Aging at the University of Arkansas for Medical Sciences, who has researched muscle protein synthesis and is also a certified strength and conditioning specialist.

Church equates workouts to a hurricane that can damage those brick buildings of your muscles. The storm blows through, and some of the bricks fall out or get broken. “That’s kind of what your muscle would look like after a workout,” he says. “You don’t get a completely flattened building, but you have pieces that are damaged.”

As this normal micro-damage happens to your muscles from exercise (and other stressors), new amino acids are popped in to replace them, thereby making muscle protein.

A hurricane, obviously, is pretty intense. And the intensity of your workout, the type of exercise you do, and how long you do it all affect MPS, explains sports nutritionist Laurent Bannock , creator of the Fueling Greatness podcast and blog , who has researched muscle protein synthesis and has a doctorate in sports nutrition. “Going for a walk is not going to stimulate much muscle protein synthesis, whereas bench pressing, deadlifting, interval training, repeated hill climbs will cause a lot of stress to the muscle tissue, and that stress elicits a much bigger response.”

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The process of muscle protein synthesis is always happening —muscle in your body is constantly breaking down and being built—but exercise is like a dimmer switch that can turn up muscle protein synthesis, Church explains. “Exercise is the most potent natural stressor we have to enhance muscle adaptation,” he says.

When you exercise regularly , your body is constantly replacing your protein building blocks. “The body is effectively going to adapt so it can handle that stress more robustly, which is why you get bigger, faster, stronger,” Bannock says.

But it simply won’t work without the protein you eat . “If you’re not taking in any dietary protein, then you’re not getting any amino acids into the body to replace the old ones,” Church says. “You have to provide the body amino acids to make new muscle.” 

Exactly how much protein you need varies on a few factors (more on that below!), but generally, “the more physically active you are, the greater your protein needs are,” Church says.

There’s no overnight shortcut to bigger, stronger muscles—just like it takes time to lay enough bricks to build an entire structure. But there are some steps you can take to support MPS so you get the most out of your workouts:

1. Time Your Protein Properly

Research has long suggested your muscles are more sensitive to dietary protein for about 48 hours after exercise. Upping your dietary protein intake during this anabolic window might increase MPS, according to the International Sports Sciences Association . That, in turn, could have some small benefits for performance if you’re an elite athlete, Bannock says.

For the rest of us, it’s practical to eat after exercise , even if our livelihoods don’t depend on shaving a few seconds off our marathon times: For starters, you’re probably hungry anyway, Bannock says, and you might be less likely to forget to properly fuel up if you make eating protein part of your post-workout routine .

Eating some protein after a workout also helps you spread your protein intake across your meals and snacks throughout the day, rather than topping off your protein stores all at once. That’s a good thing, because protein isn’t stored in your body like fat and carbs are, Bannock says. Replenishing your protein stores evenly throughout the day is also linked with faster MPS, according to a small study in The Journal of Nutrition .

2. Eat Enough Protein

Daily protein goals for building muscle can be pretty high. “Over the years, studies have recommended evenly distributing protein at about 25–40 grams per meal every three to four hours to optimize muscle protein synthesis,” says registered dietitian nutritionist Yasi Ansari , RDN, a spokesperson for the Academy of Nutrition and Dietetics.

Those benchmarks come from equations that calculate the ideal amount of daily protein for various goals, like losing weight or building muscle. According to the International Society of Sports Nutrition , active individuals should get around 1.4–2 grams of protein per kilogram of your body weight each day to optimize recovery and build lean muscle mass. (Divide your weight in pounds by 2.2 to get your weight in kilograms.)

You might notice that’s a decent amount more than the National Academy of Medicine’s official recommended dietary allowance for the average healthy adult of just 0.8 grams of protein per kilogram of body weight each day. But you should consider that the bare minimum you need to exist; very few people (if any) would see any real muscle gains from eating that little protein, Bannock says.

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On the individual level, your age, body size, health status, and activity level, among other factors, all affect how much protein you need each day, Ansari says. For example, if you’re doing a lot of cardio exercise, you can aim for the lower end of the range above. If you’re doing a lot of strength training or you’re over 65 (because we lose more muscle as we age), aim for the upper end, she says.

And keep in mind there may not really be a maximum: More recent research “suggests that the body may not have a specific dose or an upper limit to the amount of protein that can be used at one time to build muscle when consumed after resistance training,” Ansari says. We need more studies—particularly studies in women, according to a 2023 article in the Scandinavian Journal of Medicine & Science in Sports —to “truly understand and determine protein recommendations to support optimal athletic performance,” she says.

Not sure what all that means for you? Talk to your doctor or a registered dietitian about your protein needs and how to safely increase your protein intake. They can “assess your food preferences and consider your health history and activity level, and provide evidence-based protein recommendations based on your individual needs,” Ansari says. 

And if you do decide to track your protein intake, try not to get too overwhelmed by the numbers, Bannock says. “You don’t need to be counting [every] gram of protein, you just need to be roughly right,” he says. “The most important thing is the total amount of protein that you get on any day, and on average throughout the week and months and years. Getting it wrong occasionally is not really going to be an issue.”

3. Pick Nutritious, Protein-Rich Foods

From a general standpoint, Ansari recommends getting 25 grams of protein in each meal or snack from a variety of high-quality sources like eggs, poultry, nuts, legumes, and seafood, and “not going more than three to four hours without eating throughout the day to support MPS.”

What does that look like? Here are a few of her go-to examples of foods that deliver 25–40 grams of protein:

1 cup of ground turkey

5 ounces of chicken

1.5 cups of Greek yogurt topped with granola

5–6 ounces of cooked salmon

1 can of white tuna

1.5 cups of baked tofu, edamame, or black beans

Fruit smoothie with protein powder, milk, fresh fruit, and chia seeds

3 eggs with sauteed chicken sausage

Protein powders, shakes, and bars can work in a pinch, but read ingredient lists and nutrition facts carefully. Many are loaded with sugar and are higher in calories than you might need, depending on the intensity of your workout, Bannock says. It’s also worth checking to see if your go-to pick is in the National Sanitation Foundation’s Certified for Sport® directory . And don’t forget that there are plenty of plant-based protein options for vegetarians, too!

4. Don’t Skimp on Rest

While exercise and diet are the two big players in MPS , you can’t build muscle without rest and recovery. 

While you’re always experiencing some degree of muscle protein synthesis, the most notable muscle growth “occurs over a period of time while you’re recovering,” Bannock says. If you don’t give yourself time to recover—either with full rest days or by varying your training sessions day to day—“you’ll end up with a depreciating set of benefits, because your stress has exceeded the body’s ability to recover and replace and regenerate,” he says.

You also need to get plenty of sleep , Church says. “If you don’t sleep, the ability to repair the brick walls is greatly reduced.”

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Muscle protein synthesis is how your body turns dietary protein into muscle all over your body. Your workouts cause damage to your muscles, and the protein you eat gets used to repair that damage and build your muscles back even stronger than before.

Getting enough protein is key to this process, especially if you’re looking to get stronger or faster. But as long as you’re eating around 25–40 grams of protein at each of your meals and snacks, you probably don’t have to worry too much about counting every single gram.

This content is for informational and educational purposes only and does not constitute individualized advice. It is not intended to replace professional medical evaluation, diagnosis, or treatment. Seek the advice of your physician for questions you may have regarding your health or a medical condition. If you are having a medical emergency, call your physician or 911 immediately.

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• Published: 21 August 2024

Catalytic asymmetric synthesis of meta benzene isosteres

• Mingkai Zhang   ORCID: orcid.org/0000-0001-5343-1742 1 ,
• Matthew Chapman   ORCID: orcid.org/0000-0001-6449-217X 1 ,
• Bhagyesh R. Sarode   ORCID: orcid.org/0000-0001-9998-2451 2 ,
• Bingcong Xiong   ORCID: orcid.org/0009-0007-9602-5489 1 ,
• Hao Liang 1 ,
• James K. Chen   ORCID: orcid.org/0000-0002-9220-8436 2 , 3 , 4 ,
• Eranthie Weerapana   ORCID: orcid.org/0000-0002-0835-8301 1 &
• James P. Morken   ORCID: orcid.org/0000-0002-9123-9791 1  

Nature ( 2024 ) Cite this article

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• Asymmetric catalysis
• Asymmetric synthesis
• Small molecules

Although aromatic rings are common elements in pharmaceutically active compounds, the presence of these motifs brings several liabilities with respect to the developability of a drug 1 . Nonoptimal potency, metabolic stability, solubility and lipophilicity in pharmaceutical compounds can be improved by replacing aromatic rings with non-aromatic isosteric motifs 2 . Moreover, whereas aromatic rings are planar and lack three-dimensionality, the binding pockets of most pharmaceutical targets are chiral. Thus, the stereochemical configuration of the isosteric replacements may offer an added opportunity to improve the affinity of derived ligands for target receptors. A notable impediment to this approach is the lack of simple and scalable catalytic enantioselective syntheses of candidate isosteres from readily available precursors. Here we present a previously unknown palladium-catalysed reaction that converts hydrocarbon-derived precursors to chiral boron-containing nortricyclanes and we show that the shape of these nortricyclanes makes them plausible isosteres for meta disubstituted aromatic rings. With chiral catalysts, the Pd-catalysed reaction can be accomplished in an enantioselective fashion and subsequent transformation of the boron group provides access to a broad array of structures. We also show that the incorporation of nortricyclanes into pharmaceutical motifs can result in improved biophysical properties along with stereochemistry-dependent activity. We anticipate that these features, coupled with the simple, inexpensive synthesis of the functionalized nortricyclane scaffold, will render this platform a useful foundation for the assembly of new biologically active agents.

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Crystal structure data for compound 20 have been deposited at the Cambridge Structure Data Centre ( CCDC 2325329 ). Mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium through the PRIDE 50 partner repository with the dataset identifier PXD051400 . All other data are available in the main text or in the  Supplementary Information .

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Acknowledgements

We thank B. Li and T. Jayasundera of Boston College for assistance with X-ray structure analysis and NMR spectroscopy, respectively. Funding from the National Institutes of Health R35GM127140 (J.P.M.), R35GM127030 (J.K.C.), R35GM134694 (E.W.), S10OD026910 (Boston College), National Science Foundation MRI Award CHE2117276 (Boston College) and a Lamattina Fellowship (H.L.).

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Department of Chemistry, Boston College, Chestnut Hill, MA, USA

Mingkai Zhang, Matthew Chapman, Bingcong Xiong, Hao Liang, Eranthie Weerapana & James P. Morken

Department of Chemical and Systems Biology, Stanford University, Stanford, CA, USA

Bhagyesh R. Sarode & James K. Chen

Department of Developmental Biology, Stanford University, Stanford, CA, USA

James K. Chen

Department of Chemistry, Stanford University, Stanford, CA, USA

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M.Z. and J.P.M. conceptualized the study; M.Z. and M.C. conducted the synthetic investigation; H.L. performed the density functional theory calculations; B.X. and E.W. studied the hydrolase inhibition; B.R.S. and J.K.C. investigated the Hh inhibition; J.P.M. assisted with the writing of the initial draft; and all authors contributed to the review and editing of the paper.

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Correspondence to James K. Chen , Eranthie Weerapana or James P. Morken .

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J.P.M., M.Z. and H.L. declare that provisional patent applications have been filed on boron-containing cyclic molecules (US provisional application 63/509,173 and international patent application PCT/US24/34873). All other authors have no competing interests.

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Zhang, M., Chapman, M., Sarode, B.R. et al. Catalytic asymmetric synthesis of meta benzene isosteres. Nature (2024). https://doi.org/10.1038/s41586-024-07865-4

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