An overview of the bacterial SsrA system modulating intracellular protein levels and activities

In bacteria, the truncated forms of mRNAs, which usually lack a stop codon, are occasionally generated by premature termination of gene transcription and/or endo- or exonucleolytic cleavage events. Ribosomes proceeding on these molecules stall at the 3' end of the chain and are rescued by a widely distributed mechanism known as trans-translation, which includes two essential elements, ssrA RNA (a special RNA) and SmpB (a small protein). Through this mechanism, the polypeptides translated from truncated mRNAs are marked by a short peptide, known as SsrA tag, at their C-termini and directed to the specific endogenous proteases for C-terminal proteolysis. Based on the deep understanding of the SsrA tagging and degradation mechanisms, recently a series of SsrA-based genetic tools have been developed for gene regulation on the level of post-translation. They are successfully applied for controllable regulation of biological circuits in bacteria. In the present article, we systematically summarize the history, structural characteristics, and functional mechanisms of the SsrA tagging and degrading machineries, as well as their technical uses and limitations.Key Points• SsrA system plays an important role in ribosome rescue in bacteria.• SsrA-based genetic tools are useful for controlling protein levels and activities.