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The SsrA (tmRNA) Quality Control System Ribosomes stall at the 3' ends of truncated mRNAs that lack in-frame stop codons. All eubacteria possess a remarkable quality control system, the SsrA peptide tagging system, that rescues these stalled ribosomes. SsrA (or tmRNA, for transfer-messenger RNA) is a stable RNA molecule that is recruited to distressed ribosomes, and acts first as a tRNA to add a non-coded alanine residue to the nascent peptide, then functions as an mRNA to direct the addition of a short peptide degradation tag. SsrA activity results in 1) the release of stalled ribosomes from damaged messages so that they may recycle, and 2) the targeting of incompletely-synthesized polypeptides for proteolysis.
The transfer-messenger RNA (tmRNA) model of SsrA activity in ribosome rescue. Translational pause events on full-length mRNAs also lead to SsrA recruitment and ribosome rescue. We are interested in identifying and characterizing the determinants and molecular mechanisms of translational pausing. In particular, we would like to understand how nascent polypeptide chains are able to elicit translational pausing. Ribosome Pausing and A-site mRNA Cleavage Our recent results show that ribosome pausing during translation termination can lead to cleavage of the A-site mRNA codon. This nucleolytic cleavage is very unusual because the ribosome typically protects A-site mRNA from soluble RNases. The ribosome and translational pausing are required for cleavage to occur and our working model is that the ribosome itself is the A-site nuclease. Current work is focused on demonstrating that the ribosome has such activity and on characterizing the requirements for the A-site cleavage reaction
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