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Review
. 2017 Mar 19;372(1716):20160183.
doi: 10.1098/rstb.2016.0183.

Ribosome pausing, arrest and rescue in bacteria and eukaryotes

Allen R Buskirk  1 , Rachel Green  2
Affiliations
Review

Ribosome pausing, arrest and rescue in bacteria and eukaryotes

Allen R Buskirk et al. Philos Trans R Soc Lond B Biol Sci. .

Abstract

Ribosomes translate genetic information into polypeptides in several basic steps: initiation, elongation, termination and recycling. When ribosomes are arrested during elongation or termination, the cell's capacity for protein synthesis is reduced. There are numerous quality control systems in place to distinguish between paused ribosomes that need some extra input to proceed and terminally stalled ribosomes that need to be rescued. Here, we discuss similarities and differences in the systems for resolution of pauses and rescue of arrested ribosomes in bacteria and eukaryotes, and how ribosome profiling has transformed our ability to decipher these molecular events.This article is part of the themed issue 'Perspectives on the ribosome'.

Keywords: Dom34/PELO; EFP; Hbs1/HBS1l; Rli1/ABCE1; eIF5A; tmRNA.

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Figures

Figure 1.
Figure 1.
A comparison of termination and recycling mechanisms in bacteria and eukaryotes. In bacteria (left), release factors 1 and 2 recognize stop codons and hydrolyse the peptidyl-tRNA bond. Release factor 3 enhances the rate of release of RF1 or RF2. With the deacylated tRNA in the P/E hybrid state, ribosome recycling factor (RRF) and EFG bind and catalyse the dissociation of the ribosomal subunits. In eukaryotes, eRF1 and eRF3 bind the ribosome as a complex, eRF3 is released and eRF1 hydrolyses the peptidyl–tRNA bond. Following peptide release, eRF1 remains bound and, together with the ATPase Rli1/ABCE1, promotes the dissociation of ribosomal subunits.
Figure 2.
Figure 2.
Elongation pausing (left) versus arrest (right): a function of A-site occupancy. Certain conditions stall ribosomes reversibly, such as the pauses on consecutive proline codons that are resolved productively by EFP and eIF5A. When cells are starved of specific amino acids, uncharged tRNAs accumulate in the ribosomal A site. In neither case is the A site available to the surveillance machinery. Ribosomes may also pause on non-optimal codons while waiting for cognate aminoacyl-tRNA. Under these conditions, ribosomes may continue translation as charged tRNAs become available. However, with an unoccupied A site, ribosomes stalled on non-optimal codons or with truncated mRNA become substrates for the rescue machinery as the cell deems them irreversibly arrested. These rescue events lead to degradation of the incomplete protein product and of the mRNA.
Figure 3.
Figure 3.
Mechanisms of ribosome rescue on truncated mRNA. In bacteria (top), tmRNA and SmpB enter the empty A site and tmRNA accepts the nascent peptide (not shown). As the complex translocates into the P site, the tmRNA ORF is positioned for translation to resume using tmRNA as a template. Following synthesis of the SsrA-tag that targets the nascent peptide for proteolysis, regular release and recycling factors function normally at the tmRNA-encoded stop codon. In eukaryotes, the proteins Dom34, Hbs1 and Rli1 target ribosomes with truncated mRNA, catalysing the splitting of the subunits. When the peptidyl-tRNA remains with the large subunit, the ribosome quality control complex (RQC) can add an Ala/Thr-rich tail to the C-terminus (a CAT-tail) and ubiquitin moieties to internal Lys residues to target the nascent peptide for proteolysis.
See this image and copyright information in PMC

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