Report

Translational termination without a stop codon

See allHide authors and affiliations

Science  16 Dec 2016:
Vol. 354, Issue 6318, pp. 1437-1440
DOI: 10.1126/science.aai9127

You are currently viewing the abstract.

View Full Text

Rescuing stalled ribosomes

A small percentage of bacterial mRNAs lack a stop codon. Ribosomes stall at the end of such mRNAs, and the buildup of stalled ribosomes can be lethal. The primary rescue mechanism, in which translation continues on a piece of RNA that contains a stop codon, is a drug target. However, bacteria have another backup plan. James et al. present structures that show that ArfA (alternative rescue factor A) substitutes for a stop codon by binding in the ribosomal mRNA channel and recruiting RF2 (release factor 2). It mediates conformational changes required for RF2 to catalyze peptide release.

Science, this issue p. 1437

Abstract

Ribosomes stall when they encounter the end of messenger RNA (mRNA) without an in-frame stop codon. In bacteria, these “nonstop” complexes can be rescued by alternative ribosome-rescue factor A (ArfA). We used electron cryomicroscopy to determine structures of ArfA bound to the ribosome with 3′-truncated mRNA, at resolutions ranging from 3.0 to 3.4 angstroms. ArfA binds within the ribosomal mRNA channel and substitutes for the absent stop codon in the A site by specifically recruiting release factor 2 (RF2), initially in a compact preaccommodated state. A similar conformation of RF2 may occur on stop codons, suggesting a general mechanism for release-factor–mediated translational termination in which a conformational switch leads to peptide release only when the appropriate signal is present in the A site.

View Full Text