Selective Translation of Leaderless mRNAs by Specialized Ribosomes Generated by MazF in Escherichia coli

SummaryEscherichia coli (E. coli) mazEF is a stress-induced toxin-antitoxin (TA) module. The toxin MazF is an endoribonuclease that cleaves single-stranded mRNAs at ACA sequences. Here, we show that MazF cleaves at ACA sites at or closely upstream of the AUG start codon of some specific mRNAs and thereby generates leaderless mRNAs. Moreover, we provide evidence that MazF also targets 16S rRNA within 30S ribosomal subunits at the decoding center, thereby removing 43 nucleotides from the 3′ terminus. As this region comprises the anti-Shine-Dalgarno (aSD) sequence that is required for translation initiation on canonical mRNAs, a subpopulation of ribosomes is formed that selectively translates the described leaderless mRNAs both in vivo and in vitro. Thus, we have discovered a modified translation machinery that is generated in response to MazF induction and that probably serves for stress adaptation in Escherichia coli.

Graphical AbstractFigure optionsDownload high-quality image (393 K)Download as PowerPoint slideHighlights
► MazF activity causes ribosome heterogeneity in response to stress
► MazF generates a subpopulation of ribosomes selective for leaderless mRNAs
► MazF cuts upstream of AUG start codons, generating specific leaderless mRNAs
► Thus, MazF triggers a posttranscriptional stress response pathway in bacteria