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

Sylvain Durand,Anne-Catherine Helfer,Ciarán Condon,Frédérique Braun,Pascale Romby

doi:10.7554/elife.23602

Abstract

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.

Highlights

Post-transcriptional regulation is a rapid and efficient way to modulate gene expression used by all organisms
In searching for additional direct targets of RoxS that may not have been expressed under the experimental conditions of the first study, we found that RoxS potentially interacts with the extreme 5’-end of the yflS mRNA, encoding a malate transporter in B. subtilis
In a previous study we showed that RoxS, either directly or indirectly, negatively regulates the expression of up to a hundred genes, including two mRNAs encoding proteins involved in central carbon metabolism: ppnkB and sucCD (Durand et al, 2015a)

Summary

Introduction

Post-transcriptional regulation is a rapid and efficient way to modulate gene expression used by all organisms In bacteria, this regulation can involve cis-acting regulatory elements such as riboswitches, which bind small molecules and modify transcription elongation, translation or mRNA stability. This regulation can involve cis-acting regulatory elements such as riboswitches, which bind small molecules and modify transcription elongation, translation or mRNA stability It can involve trans-acting factors such as proteins (RNases or RNA binding proteins) and small regulatory RNAs (sRNAs). B. subtilis, on the other hand, has replaced RNase E by an enzyme with similar properties called RNase Y and has the additional option of exonucleolytically degrading RNAs from the 5’ end using an enzyme called RNase J1 (Mathy et al, 2007). B. subtilis shares features with the eukaryotic model of RNA decay and this observation has obscured some of the traditional divisions between « prokaryotic » and « eukaryotic » pathways of RNA degradation

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