Abstract Cells must recycle stalled ribosomes while preventing the accumulation of aberrant nascent chains. In bacteria, this is achieved by overlapping pathways with distinct substrates: ribosome-rescue systems act mainly on non-stop mRNAs, whereas ribosome-associated quality control (RQC) targets mid-ORF arrests. Work in Gram-positive bacteria defined an RQC mechanism that appends C-terminal degrons to stalled peptides, yet the full set of bacterial substrates and splitting factors remains unresolved, and enteric bacteria notably lack a canonical RQC elongation factor. This review traces the field from the discovery of tmRNA (also known as 10Sa RNA or SsrA RNA) through alternative rescue pathways to the current bacterial RQC framework. I summarize mechanisms across three layers—processing of 50S–peptidyl-tRNA, collision sensing and splitting, and downstream proteolysis—and compare species-level strategies and conservation patterns. I highlight how rescue and quality control intersect during phage infection, and outline key mechanistic uncertainties and experiments needed to resolve them.
Hiraku Takada (Fri,) studied this question.