A conserved RNA seed-pairing domain direct s small RNA-mediated stress resistance in enterobacteria

Small regulatory RNAs (sRNAs) are crucial components of many
stress response systems. The envelope stress response (ESR) of
Gram-negative bacteria is a paradigm for sRNA-mediated stress
management and involves, among other factors, the alternative
sigma factor E (r
E
) and one or more sRNAs. In this study, we identi-
fied the MicV sRNA as a new member of the r
E
regulon in Vibrio
cholerae. We show that MicV acts redundantly with another sRNA,
VrrA, and that both sRNAs share a conserved seed-pairing domain
allowing them to regulate multiple target mRNAs. V. cholerae lack-
ing r
E
displayed increased sensitivity toward antimicrobials, and
over-expression of either of the sRNAs suppressed this phenotype.
Laboratory selection experiments using a library of synthetic sRNA
regulators revealed that the seed-pairing domain of r
E
-dependent
sRNAs is strongly enriched among sRNAs identified under
membrane-damaging conditions and that repression of OmpA is
crucial for sRNA-mediated stress relief. Together, our work shows
that MicV and VrrA act as global regulators in the ESR of
V. cholerae and provides evidence that bacterial sRNAs can be
functionally annotated by their seed-pairing sequences.