20 During Translation Chain Elongation Continues Until

In this explainer, we will learn how to describe the process of translation and outline the roles of mRNA, tRNA, and ribosomes.

Ricin is a highly potent poison that can be extracted from the seeds of the castor oil plant (the seeds are shown below).

Figure 1

A dose of ricin the size of a few grains of table salt can kill an adult human! In fact, ricin has been used numerous times throughout history in various assassination attempts, including one incident involving a modified umbrella to shoot a tiny pellet of ricin!

So how does ricin work? Ricin inhibits the translation of proteins from the mRNA. If the cell cannot produce proteins, then all metabolism ends and the cells die.

A gene is a section of DNA that codes for a particular functional unit, for instance, a protein. You will recall that, in order for a gene to be expressed as a protein, it first must be transcribed to the mRNA. This mRNA is then translated, in a process called translation, to a polypeptide chain. A polypeptide is a long chain of amino acids (the building blocks of proteins). This polypeptide chain, in association with other chains, can then fold into the corresponding protein for that gene.

Definition: Messenger RNA (mRNA)

An mRNA is a message that is transcribed from the DNA of a gene and that can be translated to make the corresponding protein.

Definition: Translation

Translation is the process of converting an mRNA sequence into a polypeptide that can fold into a protein.

Definition: Polypeptide

A polypeptide is a single linear chain of amino acids that are held together by peptide bonds. A polypeptide can fold into a protein with a specific function.

Definition: Amino Acid

Amino acids are the individual monomers that together make up a protein. An amino acid contains an amino group, a carboxyl group, and a side chain that varies between the 20 different standard amino acids.

In eukaryotic cells, the mRNA is transcribed in the nucleus and then exits through the nuclear pores into the cytoplasm, where translation occurs. In prokaryotic cells, which do not have nuclei, transcription and translation take place in the cytoplasm.

The translation of an mRNA into a polypeptide involves converting the mRNA sequence into the appropriate amino acids. You will recall that sequences of 3 nucleotides make up what are called codons. Each codon can code for a specific amino acid based on the genetic code.

You will recall that mRNA sequences are read in the to direction. For example, consider the following mRNA sequence

The two codons "AUG" and "UUC" code for the amino acids methionine (Met) and phenylalanine (Phe). You can decode any mRNA sequence by using a codon wheel, as shown in Figure 2.

Key term: Codon

A codon is a sequence of three nucleotides of DNA or RNA that corresponds to a specific amino acid.

Key term: 5′ and 3′

By convention, DNA sequences are written in the (five prime) to (3 prime) direction, which is the same direction that DNA is synthesized in. These numbers refer to the specific carbon in the deoxyribose backbone of DNA to which a new deoxyribonucleotide bonds.

Example 1: Understanding the Purpose of Translation

What is the purpose of translation?

1. To convert a sequence of DNA into a sequence of mRNA
2. To form a protein from multiple polypeptide chains
3. To convert a sequence of mRNA into a sequence of amino acids
4. To convert a sequence of mRNA into a sequence of DNA
5. To convert a sequence of amino acids into a sequence of RNA nucleotides

Answer

In order for a gene in DNA to be converted into a protein, first, the messenger RNA (mRNA) must be formed in a process called transcription. This mRNA sequence can then be translated into a sequence of amino acids to form a polypeptide in a process called translation. The resulting polypeptide can fold to form the corresponding protein for the gene.

Let's look at the different answers to see which description best matches the purpose of translation.

Option A, to convert a sequence of DNA into a sequence of mRNA, is incorrect. This is actually describing the process of transcription!

Option B, to form a protein from multiple polypeptide chains, is incorrect. This is how a quaternary protein structure can be formed. Although this relates to translation, this is not the purpose of translation.

Option C, to convert a sequence of mRNA into a sequence of amino acids, is correct. This is exactly what the purpose of translation is.

Option D, to convert a sequence of mRNA into a sequence of DNA, is incorrect. This is describing the process of reverse transcription.

Option E, to convert a sequence of amino acids into a sequence of RNA nucleotides, is incorrect. This is not something that is done in biological systems.

Therefore, the correct answer is option C, to convert a sequence of mRNA into a sequence of amino acids.

Example 2: Determine the Sequence of Amino Acids From mRNA

Consider the following sequence of mRNA:

Use the codon wheel provided to determine the sequence of amino acids that this mRNA sequence will be translated into.

1. Tyr, Asp, Gln, Pro
2. Ser, Gly, Gln, Ser
3. Tyr, Glu, Asn, Arg
4. Stop, Asp, Lys, Pro
5. His, Glu, Thr, Arg

Answer

In order for a gene in DNA to be converted into protein, first, the messenger RNA (mRNA) must be formed in a process called transcription. Transcription produces a sequence of mRNA that carries the same information that is in the DNA of the gene but is RNA, so it includes uracil (U) in place of thymine (T). This mRNA sequence can then be translated into amino acids to form a polypeptide in a process called translation. The resulting polypeptide can fold to form the corresponding protein for the gene.

A codon wheel, as shown above, is the genetic code for codons and the corresponding amino acid. To use it, start from the center of the wheel (at the end) and work your way out (toward the end). You will recall that mRNA sequences are read in the to direction by convention. So, for the codon -GAG- , you will work through the codon wheel starting from the center and will choose "G," then "A" in the next area, then "G" in the next area. This gives the amino acid Glu.

The provided sequence can be broken up into codons after the third nucleotide, which corresponds to UAC GAG AAC CGA. Let's look at how each codon translates to its amino acid:

• UAC: Tyr,
• GAG: Glu,
• AAC: Asn,
• CGA: Arg.

Therefore, the correct answer is option C, Tyr, Glu, Asn, Arg.

There are two major components in translation: transfer RNAs and ribosomes. Let's look at each one in some detail.

A transfer RNA (tRNA) is a specialized adapter RNA molecule that is able to bring amino acids to the site of translation for synthesis. For each codon and amino acid, there is a corresponding tRNA that goes with it. All tRNA molecules have the same distinct characteristic cloverleaf shape that you can see in Figure 3. This distinct shape is due to the single-stranded RNA being able to fold upon itself due to complementary base pairing rules.

Definition: Transfer RNA (tRNA)

A tRNA is an adapter molecule that carries amino acids to the ribosome for translation.

Each tRNA has two specialized regions.

On one end is the anticodon loop at the bottom of the molecule (Figure 3). This region is complementary to the codon sequence that is on the mRNA. Because it is complementary, the anticodon can base pair with the codon in the mRNA. This is how a tRNA can interact specifically with the codons in an mRNA. For example, the anticodon AUU (as in Figure 3) can bind to the complementary mRNA codon AAU—this is shown in Figure 4 with the anticodon shown in the to direction.

On the other end of the tRNA (at the top) is where the corresponding amino acid is bound. In our example, AAU is the codon for asparagine (Asn), so this tRNA will be carrying an asparagine amino acid.

Definition: Anticodon

An anticodon is the complementary sequence to a codon in an mRNA that is found in a tRNA.

Besides the tRNA, the other major component of translation is a large protein and RNA complex called a ribosome. This complex is a macromolecular machine that can work together with tRNAs to convert the mRNA into polypeptides. It does this by reading each section of the mRNA molecule to decode the sequence by bringing together the appropriate amino acids (carried by the tRNA) and forming a covalent bond (a peptide bond) between them. The resulting polypeptide can then fold into a protein.

Definition: Ribosome

Ribosomes are large protein and RNA complexes that perform the translation of mRNA to synthesize polypeptides.

Example 3: Understanding the Purpose of the tRNA

What is the purpose of tRNA in the process of translation?

1. To provide the site within a eukaryotic cell for translation to take place
2. To carry amino acids to the mRNA molecule being translated to form a polypeptide chain
3. To catalyze the formation of peptide bonds between amino acids in a polypeptide chain
4. To provide the sequence of nucleotides that determine the sequence of amino acids

Answer

Translation is the process of converting an mRNA into the corresponding polypeptide.

The site of translation is the ribosome. Transfer RNAs (tRNAs) assist in bringing the corresponding amino acids (as indicated by the mRNA) into place so the ribosome can form a peptide bond to join amino acids. A tRNA has an anticodon loop that is able to hydrogen bond to its complementary codon sequence on the mRNA.

Let's look at the different answers to see which one best describes the purpose of the tRNA during translation.

Option A, to provide the site within a eukaryotic cell for translation to take place, is incorrect. The site for translation is the ribosome, not the tRNA.

Option B, to carry amino acids to the mRNA molecule being translated to form a polypeptide chain, is correct. This is what the purpose of the tRNA is during translation.

Option C, to catalyze the formation of peptide bonds between amino acids in a polypeptide chain, is incorrect. This is referring to the peptidyl transferase enzyme activity of the ribosome.

Option D, to provide the sequence of nucleotides that determine the sequence of amino acids, is incorrect. This is describing how the genetic code can be used to determine the corresponding amino acid.

Therefore, the correct answer is option B, to carry amino acids to the mRNA molecule being translated to form a polypeptide chain.

Let's talk a bit about the structure of the ribosome.

The ribosome is made up of two subunits called the large subunit and the small subunit, as you can see in Figure 5. When they are not translating, the two subunits separate and exist in the cytoplasm until another strand of mRNA needs to be translated.

The ribosomal subunits are composed of protein and RNA. The RNA is a specialized kind of RNA called ribosomal RNA or rRNA. Assembly of ribosomes is done in the nucleolus in eukaryotic cells, where hundreds of thousands of ribosomes can be assembled in one hour! Once the subunits of the ribosomes are assembled, they move to the cytoplasm where they can perform translation.

Now that we have seen the two major components of translation, it is time to describe how the tRNA and the ribosomes can work together to translate a sequence of mRNA into the corresponding polypeptide.

There are three major steps to translation: initiation, elongation, and termination.

During initiation, the small subunit of the ribosome first binds to the mRNA and moves along until it finds the start codon. This codon is the sequence "AUG," which corresponds to the amino acid methionine (Met). Once bound, the tRNA carrying methionine associates with the small subunit of the ribosome as shown in Figure 6.

Key term: Start Codon

The start codon signals the beginning of the protein sequence by initiating translation of mRNA by the ribosome. The most common start codon is AUG.

Once the tRNA carrying methionine binds to the start codon, the large subunit joins the small subunit, and the elongation stage of translation can begin. The large subunit contains 3 sites that the tRNA can interact with. The "A" site is the aminoacyl site, the "P" site is the peptidyl site, and the "E" site is the exit site. When the large subunit joins, the tRNA bound to the start codon will be found in the P site. The next tRNA carrying the appropriate amino acid then associates with the mRNA in the aminoacyl site. Now, the ribosome can bring together the two amino acids to form a peptide bond with its peptidyl transferase enzymatic activity located in the large ribosomal subunit. This can link the next amino acid with the previous amino acid to elongate the polypeptide. You can see the elongation step of translation in Figure 7.

Definition: Peptidyl Transferase

Peptidyl transferase is the enzymatic activity of the ribosome, and it catalyzes the formation of a peptide bond by linking amino acids to the growing polypeptide during translation.

Ricin, the poison described earlier, has enzymatic activity and can cleave or remove specific components of the ribosome that are involved in elongation. This prevents the ribosome from continuing the elongation step, and protein synthesis stops in cells.

Next, the ribosome moves in the to direction down the mRNA to the next codon. This shifts the tRNAs into new sites in the ribosome. The tRNA that had lost its amino acid in the previous step now enters the E site and exits the ribosome, the tRNA with the polypeptide chain moves into the peptidyl site, and a new tRNA that contains the amino acid for the next codon enters at the aminoacyl site. You can see this in Figure 8.

These steps repeat, and the polypeptide chain continues to elongate until a stop codon (UAA, UAG, or UGA) is reached. Translation termination is triggered by special proteins called release factors that cause the ribosome to release the polypeptide and the mRNA. The polypeptide can then go on to fold into its appropriate shape.

Key term: Stop Codon

The stop codon signals the end of the protein sequence by terminating the translation of the mRNA by the ribosome.

Example 4: Understanding the Stages of Translation

The diagram provided shows the stages of translation in an incorrect order. Order the stages correctly.

Answer

Translation is the process of converting an mRNA into the corresponding polypeptide.

The site of translation is the ribosome, which is made up of two subunits (a small subunit and a large subunit). Transfer RNAs (tRNAs) assist in bringing the corresponding amino acids (as indicated by the mRNA) into place so the ribosome can form a peptide bond to join amino acids. A tRNA has an anticodon loop that is able to hydrogen bond to its complementary codon sequence on the mRNA.

This process starts with the small subunit of the ribosome binding to the end of the mRNA. Next, the tRNA for that codon enters the ribosome and binds to the mRNA with its complementary anticodon. The large subunit of the ribosome next joins the small subunit. The next tRNA with a complementary anticodon binds to the following codon on the mRNA. Once brought together, the ribosome can join the two amino acids together with a peptide bond. The ribosome then moves along and releases the first tRNA (which is now free of an amino acid) to let another tRNA that is complementary to the next codon enter. This process of elongation continues until a stop codon is reached, and the ribosome releases the polypeptide and mRNA.

Therefore, the correct sequence is W, V, Z, Y, X.

Polypeptides can be synthesized relatively quickly at a rate of about 10 amino acids per second. For perspective, the protein insulin is made up of two polypeptides that together are about 50 amino acids long, and this would take a ribosome about 5 seconds to synthesize! In addition, a single mRNA can be translated by numerous ribosomes, in a structure called a polysome or polyribosome, to allow for simultaneous synthesis of a single polypeptide. Once the mRNA is translated, it can be reused for further translations until the mRNA is eventually degraded.

Let's recap some of the key points we have covered in this explainer.

Key Points

• Translation is the process of converting a sequence of mRNA into a polypeptide.
• The site of protein synthesis is the ribosome in the cytoplasm.
• tRNA is able to bring amino acids to the ribosome for translation.
• Translation goes through several stages in order to elongate a polypeptide.
• The initiation stage involves the binding of the ribosome to the mRNA.
• The elongation stage involves extending the polypeptide chain.
• The termination stage occurs once a stop codon is reached, and the ribosome and polypeptide dissociate with the aid of release factors.

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