Regulation of Caulobacter development by trans‐translation

tmRNA is a specialized RNA that has the unique ability to mediate the addition of a peptide tag to the C terminus of nascent proteins before they are released from the ribosome. In a reaction known as trans ‐translation, tmRNA enters substrate ribosomes and acts both as a tRNA and an mRNA, first accepting the nascent polypeptide, and then encoding the peptide tag that is added by the ribosome. The peptide tag targets the protein for rapid proteolysis, and the substrate ribosome is released. tmRNA and its accessory protein, SmpB, have been found in all bacteria, and are required for proliferation and differentiation in many systems. Caulobacter crescentus mutants that lack the trans ‐translation pathway have a defect in the cell cycle and do not initiate DNA replication at the correct time. Through identification of the substrates of trans ‐translation in C. crescentus and investigation of the mechanisms by which substrates are selected, we have shown that trans ‐translation is required for post‐transcriptional regulation of gene expression. The abundance and localization of tmRNA and SmpB are precisely controlled in order to coordinate this regulation with the cell cycle and other physiological events.