13. During translation when release factor binds to stop codon on m-RNA in A-site of ribosome, the synthesized translation peptide transferred to
    (1) t-RNA            (2) Water
    (3) H⁺(4) Amino acids

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Introduction

Protein synthesis, or translation, is a fundamental process in all living cells, culminating in the production of functional proteins. The final stage of translation is termination, triggered when the ribosome encounters a stop codon in the mRNA. At this critical juncture, a specialized molecule called a release factor binds to the stop codon, prompting the release of the newly synthesized polypeptide chain. But where does the peptide go? This article explores the molecular details of translation termination and explains why the synthesized peptide is ultimately transferred to water.

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Overview of Translation Termination

Translation termination is the process by which the ribosome recognizes a stop codon (UAA, UAG, or UGA) in the mRNA and releases the completed polypeptide chain. This process is essential for ensuring that proteins are synthesized to the correct length and that the translation machinery is recycled for future rounds of protein synthesis.

Key Steps in Translation Termination

1. Recognition of the Stop Codon:
   When the ribosome reaches a stop codon in the A site, it signals the end of the coding sequence.

2. Binding of Release Factors:
   Release factors (RFs) bind to the stop codon in the A site. In prokaryotes, RF1 recognizes UAA and UAG, while RF2 recognizes UAA and UGA. In eukaryotes, eRF1 recognizes all three stop codons.

3. Hydrolysis of the Peptidyl-tRNA Ester Bond:
   The release factor triggers the hydrolysis of the ester bond linking the completed polypeptide to the tRNA in the P site.

4. Release of the Polypeptide:
   The polypeptide is released from the ribosome and the tRNA is ejected.

5. Dissociation of the Ribosome:
   The ribosomal subunits, mRNA, and remaining factors dissociate and are recycled for new rounds of translation.

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The Fate of the Synthesized Peptide

At the heart of termination is the question: To what is the synthesized peptide transferred when the release factor binds the stop codon? The options are:

• (1) tRNA

• (2) Water

• (3) H+

• (4) Amino acids

To answer this, we must understand the chemistry of peptide release.

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The Chemistry of Peptide Release

During elongation, the growing polypeptide chain is attached to the tRNA in the P site via an ester bond. When a stop codon is encountered, the release factor binds to the A site and induces a conformational change in the ribosome, converting the peptidyl transferase center (PTC) into an esterase.

Hydrolysis of the Peptidyl-tRNA Ester Bond

The key event is the hydrolysis of the ester bond between the polypeptide and the tRNA. This reaction is analogous to the peptide bond formation during elongation, but instead of transferring the polypeptide to an incoming aminoacyl-tRNA, the ester bond is cleaved by a water molecule.

• Nucleophile: In termination, the nucleophile is a water molecule, not the amino group of an aminoacyl-tRNA as in elongation.

• Reaction: The water molecule attacks the carbonyl carbon of the ester bond, resulting in the release of the polypeptide and the formation of a free tRNA.

• Role of the Release Factor: The release factor positions the water molecule for nucleophilic attack and stabilizes the transition state, ensuring efficient hydrolysis3.

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Why Is the Peptide Transferred to Water?

The term “transferred to water” refers to the fact that the polypeptide is released into the aqueous environment of the cell, free from any covalent attachment to tRNA or other molecules. The actual chemical event is the hydrolysis of the peptidyl-tRNA ester bond by water, resulting in the liberation of the polypeptide and the regeneration of the tRNA.

• Not Transferred to tRNA: The polypeptide is not transferred to another tRNA; instead, it is released from the tRNA.

• Not Transferred to H+ or Amino Acids: While protons (H+) are involved in the reaction mechanism (e.g., proton shuttling by the 2′-OH of the tRNA), the polypeptide is not transferred to H+ or to free amino acids.

• Not Transferred to Amino Acids: The polypeptide is not transferred to another amino acid; it is released as a complete chain.

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Molecular Mechanism: The Role of Water and the GGQ Motif

The universally conserved GGQ motif in release factors is critical for termination. This motif positions a water molecule for nucleophilic attack on the ester bond of the peptidyl-tRNA. The reaction proceeds as follows:

1. Positioning of Water:
   The release factor positions a water molecule near the ester bond of the peptidyl-tRNA.

2. Nucleophilic Attack:
   The water molecule acts as a nucleophile, attacking the carbonyl carbon of the ester bond.

3. Cleavage of the Ester Bond:
   The ester bond is hydrolyzed, releasing the polypeptide and leaving a free tRNA.

4. Proton Shuttling:
   The 2′-OH group of the tRNA’s terminal adenosine (A76) may assist in proton transfer during the reaction, but the polypeptide is not transferred to the tRNA or to protons3.

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Consequences of Termination

• Polypeptide Release:
  The newly synthesized protein is released into the cytoplasm, where it can fold into its functional structure or be targeted to specific cellular locations.

• Ribosome Recycling:
  The ribosomal subunits, mRNA, and tRNA are dissociated and recycled for new rounds of translation45.

• Quality Control:
  Proper termination ensures that only full-length, functional proteins are produced. Errors in termination can lead to truncated or misfolded proteins.

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Summary Table

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Common Misconceptions

• Peptide is transferred to tRNA:

  • Fact: The polypeptide is released from the tRNA, not transferred to another tRNA.

• Peptide is transferred to H+ or amino acids:

  • Fact: The polypeptide is released into the aqueous environment, not to protons or free amino acids.

• Release factor is an enzyme:

  • Fact: The release factor is not an enzyme but facilitates the hydrolysis reaction by positioning water and stabilizing the transition state23.

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Conclusion

When a release factor binds to a stop codon in the A site of the ribosome, the synthesized polypeptide is transferred to water. This means that the ester bond linking the polypeptide to the tRNA is hydrolyzed by a water molecule, releasing the completed protein into the cellular environment. This process is essential for the proper termination of translation and the production of functional proteins.

Correct answer:
(2) Water