The VrrA sRNA controls a stationary phase survival factor Vrp of <i>Vibrio cholerae</i>

Small non-coding RNAs (sRNAs) are emerging regulatory elements in bacteria. The <i>Vibrio cholerae</i> sRNA VrrA has previously been shown to down-regulate outer membrane proteins (OmpA and OmpT) and biofilm matrix protein (RbmC) by base-pairing with the 5′ region of the corresponding mRNAs. In this study, we present an additional target of VrrA in <i>V. cholerae</i>, the mRNA coding for the ribosome binding protein Vrp. Vrp is homologous to ribosome-associated inhibitor A (RaiA) of <i>Escherichia coli</i> which facilitates stationary phase survival through ribosome hibernation. We show that VrrA down-regulates Vrp protein synthesis by base-pairing to the 5′ region of <i>vrp</i> mRNA and that the regulation requires the RNA chaperone protein, Hfq. We further demonstrate that Vrp is highly expressed during stationary phase growth and associates with the ribosome of <i>V. cholerae</i>. The effect of the Vrp protein in starvation survival is synergistic with that of the VC2530 protein, a homolog of the <i>E. coli</i> hibernation promoting factor HPF, suggesting a combined role for these proteins in ribosome hibernation in <i>V. cholerae</i>. Vrp and VC2530 are important for <i>V. cholerae</i> starvation survival under nutrient deficient conditions. While VC2530 is down-regulated in cells lacking <i>vrrA</i>, mutation of <i>vrp</i> results in VC2530 activation. This is the first report indicating a regulatory role for an sRNA, modulating stationary factors involved in bacterial ribosome hibernation.