sRNA-mediated activation of gene expression by inhibition of 5'-3' exonucleolytic mRNA degradation

Post-transcriptional control by small regulatory RNA (sRNA) is critical for rapid adaptive processes. sRNAs can directly modulate mRNA degradation in Proteobacteria without interfering with translation. However, Firmicutes have a fundamentally different set of ribonucleases for mRNA degradation and whether sRNAs can regulate the activity of these enzymes is an open question. We show that Bacillus subtilis RoxS, a major trans-acting sRNA shared with Staphylococus aureus, prevents degradation of the yflS mRNA, encoding a malate transporter. In the presence of malate, RoxS transiently escapes from repression by the NADH-sensitive transcription factor Rex and binds to the extreme 5'-end of yflS mRNA. This impairs the 5'-3' exoribonuclease activity of RNase J1, increasing the half-life of the primary transcript and concomitantly enhancing ribosome binding to increase expression of the transporter. Globally, the different targets regulated by RoxS suggest that it helps readjust the cellular NAD⁺/NADH balance when perturbed by different stimuli.