Dynamics of diversified A-to-I editing inStreptococcus pyogenesis governed by changes in mRNA stability

Abstract

Adenosine-to-inosine (A-to-I) RNA editing plays an important role in the post-transcriptional regulation of eukaryotic cell physiology. However, our understanding of the occurrence, function and regulation of A-to-I editing in bacteria remains limited. Bacterial mRNA editing is catalysed by the deaminase TadA, which was originally described to modify a single tRNA inE. coli. Intriguingly, several bacterial species appear to perform A-to-I editing on more than one tRNA. Here, we provide evidence that in the human pathogenStreptococcus pyogenes, tRNA editing has expanded to an additional tRNA substrate. Using RNA sequencing, we identified more than 27 editing sites in the transcriptome ofS. pyogenesSF370 and demonstrate that the adaptation ofS. pyogenesTadA to a second tRNA substrate has also diversified the sequence context and recoding scope of mRNA editing. Based on the observation that editing is dynamically regulated in response to several infection-relevant stimuli, such as oxidative stress, we further investigated the underlying determinants of editing dynamics and identified mRNA stability as a key modulator of A-to-I editing. Overall, our findings reveal the presence and diversification of A-to-I editing inS. pyogenesand provide novel insights into the plasticity of the editome and its regulation in bacteria.

Expanding the genetic toolbox for the obligate human pathogenStreptococcus pyogenes

“…When comparing the maximum induction levels reached by each inducible regulatory element, the promoters Plac(1) and Plac(2) displayed the highest fold change overall (Figure 4B and E). Finally, we examined the activity of an erythromycin-sensitive riboswitch in S. pyogenes, which was successfully applied in a recent study (63). The PgyrA(Sag) promoter from Streptococcus agalactiae, together with the erythromycin-responsive 5'UTR of the ermB gene, was placed upstream of the ffluc reporter in pSpy1C.…”