10.5
Termination of Translation
The large ribosomal subunit has several important structures essential to translation. These include the peptidyl transferase center (PTC) - which is…
Once an mRNA is translated, the ribosome needs to dissociate from the RNA and release the newly made polypeptide chain.
Translation is terminated when a stop codon, UAA, UAG, or UGA, is encountered. There are no complementary tRNAs that correspond to stop codons.
Instead, when a stop codon is positioned on the A site of the ribosome, it is recognized by proteins called release factors, RF1 or RF2.
This binding forces the enzyme peptidyl transferase in the ribosome to catalyze the addition of a water molecule instead of an amino acid to the peptidyl-tRNA.
As a result, the P-site amino acid detaches from its tRNA, releasing the newly made polypeptide into the cytoplasm.
Next, a third release factor, RF3, bound to GDP joins the ribosome.
On the ribosome, RF3 replaces GDP with GTP. This exchange brings about a conformational change in RF3, which triggers the dissociation of RF1 and RF2 from the ribosome.
Then, RF3 catalyzes GTP hydrolysis, which allows the ribosomal subunits to dissociate from each other and from the mRNA.
The disassembled ribosomal subunits bound to an initiator tRNA, can now join a new mRNA for another round of translation.
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Q1: What signals the ribosome to stop protein synthesis?
Stop codons (UAA, UAG, UGA) in the mRNA signal termination of translation. When a stop codon enters the ribosomal A site, no corresponding tRNA exists to recognize it. Instead, release factors bind and catalyze hydrolysis of the bond between the polypeptide chain and the tRNA in the P site, releasing the completed protein.
Q2: How do release factors recognize stop codons?
Release factors are proteins that specifically recognize stop codons in the A site of the ribosome. They mimic the structure of tRNA but carry catalytic domains instead of amino acids. Upon stop codon recognition, release factors trigger peptidyl transferase activity to hydrolyze the ester bond linking the polypeptide to the P-site tRNA, facilitating protein release.
Q3: What happens to the ribosome after translation ends?
After the polypeptide is released, the ribosome must dissociate from the mRNA. Ribosomal subunits separate with the help of ribosome recycling factors and GTPase activity. The mRNA and deacylated tRNA are released, allowing the ribosomal subunits to be recycled for new rounds of protein synthesis.
Q4: Why is translation termination important for cell function?
Accurate termination ensures proteins are synthesized to their correct length and prevents read-through into untranslated regions. Improper termination can produce truncated or aberrant proteins that may misfold or aggregate. Proper termination also allows ribosomal subunits to be recycled efficiently, maintaining cellular protein synthesis capacity.
Q5: What are the different types of release factors in prokaryotes and eukaryotes?
Prokaryotes use RF1 and RF2 to recognize different stop codons, plus RF3 for ribosome recycling. Eukaryotes use eRF1, which recognizes all three stop codons, and eRF3, a GTPase that enhances eRF1 function. Both systems ensure efficient and accurate termination of translation.
Q6: How does the cell handle premature stop codons in mRNA?
Premature stop codons can trigger nonsense-mediated mRNA decay, a quality control mechanism that degrades aberrant transcripts. The upf proteins and nonsense mediated mrna decay pathway detect stop codons in abnormal positions and mark mRNAs for degradation, preventing synthesis of truncated proteins that could harm cellular function.
Q7: What role does GTP hydrolysis play in translation termination?
GTP hydrolysis provides energy for release factor function and ribosome recycling. When release factors bind stop codons, GTP hydrolysis drives conformational changes that activate the catalytic domain to cleave the polypeptide-tRNA bond. Additional GTP hydrolysis by recycling factors powers ribosomal subunit dissociation and mRNA release.