Translation Termination and Release Factors

Translation termination is the final phase of protein synthesis, in which the ribosome recognises a stop codon, releases the completed polypeptide, and prepares to dissociate. Release factors are the proteins that read stop codons and trigger hydrolysis of the finished chain from the last transfer RNA.

Definition

Translation termination is the release-factor-mediated recognition of a stop codon in the ribosomal A site followed by hydrolysis of the bond joining the completed polypeptide to the P-site transfer RNA, ending synthesis.

Scope

This topic covers how stop codons are recognised by class I release factors, how the completed polypeptide is released by hydrolysis at the peptidyl transferase centre, the role of class II GTPase release factors, and how the ribosome is subsequently split and recycled. It is a mechanistic topic, not clinical guidance.

Core questions

• How are stop codons recognised without a transfer RNA?
• How is the finished polypeptide released from the ribosome?
• What distinguishes class I and class II release factors?
• How is the ribosome recycled after termination?

Key concepts

• Stop codons (UAA, UAG, UGA)
• Class I release factors (eRF1; bacterial RF1/RF2)
• Class II GTPase release factors (eRF3; bacterial RF3)
• Peptidyl-tRNA hydrolysis
• Ribosome recycling
• Readthrough and nonsense suppression

Key theories

Protein decoding of stop codons

Stop codons are read not by transfer RNAs but by class I release factor proteins, which recognise the codon in the decoding centre and promote hydrolysis of the peptidyl-tRNA bond to release the protein.

Mechanisms

When a stop codon enters the ribosomal A site, a class I release factor (eRF1 in eukaryotes, RF1 or RF2 in bacteria) recognises it directly through protein-codon contacts and reaches into the peptidyl transferase centre, where it promotes hydrolysis of the ester bond linking the completed polypeptide to the P-site transfer RNA, releasing the protein. A class II GTPase release factor (eRF3, or bacterial RF3) couples GTP hydrolysis to this process and helps coordinate factor turnover. After release, ribosome recycling factors and initiation-associated factors split the ribosome into subunits and clear the remaining tRNA and mRNA, regenerating components for new rounds of initiation. The crystal structure of eRF1 revealed how a single protein can both recognise stop codons and trigger hydrolysis.

Clinical relevance

Premature stop codons arising from nonsense mutations cause many genetic diseases by truncating proteins, and the efficiency of termination versus readthrough is biologically and pharmacologically relevant, which connects this step to disease mechanisms. This entry describes molecular processes and is not a basis for individual diagnostic or treatment decisions.

Evidence & guidelines

The termination mechanism is established by biochemical, genetic, and structural studies of bacterial and eukaryotic release factors, consolidated in major review literature and standard textbooks.

History

Bacterial release factors were identified biochemically in the 1960s, distinguishing the codon-reading class I factors from the GTPase class II factor. The 2000 crystal structure of human eRF1 clarified how a protein decodes all three stop codons and links recognition to peptide release, and later structural and biochemical work defined ribosome recycling.

Key figures

• David Barford
• Haiwei Song
• Thomas Dever
• Rachel Green

Seminal works

• song-2000
• dever-2012

Frequently asked questions

Why is there no transfer RNA for stop codons?

Stop codons are recognised instead by release factor proteins; these factors read the codon and trigger release of the finished protein rather than adding another amino acid.

What happens to the ribosome after the protein is released?

After release the ribosome is recycled: dedicated factors split it into its two subunits and clear the remaining transfer RNA and messenger RNA so the components can be reused for a new round of translation.