Emerging views on tmRNA-mediated protein tagging and ribosome rescue

Transfer-messenger RNA (tmRNA), also known as SsrA or 10Sa RNA, is a bacter ial ribonucleic acid that recycles 70S ribosomes stalled on problematic mes senger RNAs (mRNAs) and also contributes to the degradation of incompletely synthesized peptides. tmRNA acts initially as transfer RNA (tRNA), being a minoacylated at its 3'-end by alanyl-tRNA synthetase, to add alanine to the stalled polypeptide chain. Resumption of translation ensues not on the mRN A on which the ribosomes were stalled but at an internal position in tmRNA. Termination soon occurs, tmRNA recruiting the appropriate termination fact ors allowing the release of the tagged protein that is subsequently recogni zed and degraded by specific cytoplasmic and periplasmic proteases, and per mits ribosome recycling. Recent data suggest that tmRNA tags bacteria[ prot eins in three other instances; when ribosomes stall at internal sites; duri ng 'readthrough' of canonical termination codons; and when ribosomes are at the termination codon of intact messages. The importance of bacteria] tmRN As for survival, growth under stress, and pathogenesis is also discussed. R ecent in vivo and in vitro studies have identified novel ligands of tmRNA. Based on the available experimental evidences, an updated model of tmRNA me diated protein tagging and ribosome rescue in bacteria is presented.