Ribosome roadblocks and traffic controllers in bacteria

SUMMARY Protein synthesis by ribosomes proceeds through the sequential stages of initiation, elongation, termination, and ribosome recycling. In most bacteria, coupled transcription-translation enhances the efficiency of transcription but limits opportunities to repair or eliminate faulty mRNAs, thereby increasing the likelihood that ribosomes encounter incomplete or damaged transcripts. Furthermore, mRNA integrity can be compromised by transcriptional errors, abortive transcription, nucleolytic cleavage, or chemical damage. Translation of such defective transcripts, as well as other hard-to-translate mRNAs, can impede elongation or termination, resulting in stalled ribosome complexes that sequester ribosomes and tRNAs, thereby reducing their availability for subsequent rounds of translation. To maintain translation capacity, bacteria employ dedicated ribosome rescue and quality control pathways that resolve stalled complexes and promote the turnover of aberrant mRNAs and nascent polypeptides. Here, we summarize the molecular mechanisms underlying bacterial ribosome stalling, describe the pathways that rescue stalled ribosomes, and discuss current technologies for detecting ribosome stalling. We also highlight the physiological roles of programmed ribosome stalling and explore the potential of ribosome rescue pathways as druggable sites.