Ribosome Collisions Trigger Ribosome Rescue in Bacteria

Ribosome rescue pathways recycle the subunits from stalled ribosomes and target the aborted nascent peptide for degradation. Building upon seminal studies in eukaryotes, recent work in bacteria shows that rescue pathways are triggered by ribosome collisions. When an upstream ribosome catches up to a stalled one, a unique interface that directly recruits rescue factors forms between them. The nuclease SmrB in Escherichia coli, for example, cleaves mRNA, targeting it for decay and triggering the rescue of upstream ribosomes by transfer-messenger RNA (tmRNA). In contrast, MutS2/RqcU in Bacillus subtilis splits stalled ribosomes into subunits without mRNA cleavage. Finally, the helicase HrpA splits stalled ribosomes in E. coli through a different mechanism. This review focuses on the discovery of these factors; the structural basis of their activities on collided disomes; and how, after splitting, the nascent chains trapped on 50S are targeted for degradation by the ribosome-associated quality control pathway.