Abstract
The RNA‐binding protein RapZ cooperates with small RNAs (sRNAs) GlmY and GlmZ to regulate the glmS mRNA in Escherichia coli. Enzyme GlmS synthesizes glucosamine‐6‐phosphate (GlcN6P), initiating cell envelope biosynthesis. GlmZ activates glmS expression by base‐pairing. When GlcN6P is ample, GlmZ is bound by RapZ and degraded through ribonuclease recruitment. Upon GlcN6P depletion, the decoy sRNA GlmY accumulates through a previously unknown mechanism and sequesters RapZ, suppressing GlmZ decay. This circuit ensures GlcN6P homeostasis and thereby envelope integrity. In this work, we identify RapZ as GlcN6P receptor. GlcN6P‐free RapZ stimulates phosphorylation of the two‐component system QseE/QseF by interaction, which in turn activates glmY expression. Elevated GlmY levels sequester RapZ into stable complexes, which prevents GlmZ decay, promoting glmS expression. Binding of GlmY also prevents RapZ from activating QseE/QseF, generating a negative feedback loop limiting the response. When GlcN6P is replenished, GlmY is released from RapZ and rapidly degraded. We reveal a multifunctional sRNA‐binding protein that dynamically engages into higher‐order complexes for metabolite signaling.
Highlights
Post-transcriptional regulation mediated by RNA and RNA-binding proteins (RBPs) has emerged as critical layer in regulation of gene expression and cellular physiology in all organisms
It remains largely unclear how sRNA-binding proteins are themselves regulated, how they are embedded in the protein–protein interaction network, and to which extent they cross-talk with transcriptional regulators
The degree of sRNA GlmZ processing is determined by availability of adaptor protein RapZ for interaction, which is in turn regulated by sRNA GlmY
Summary
Post-transcriptional regulation mediated by RNA and RNA-binding proteins (RBPs) has emerged as critical layer in regulation of gene expression and cellular physiology in all organisms. ProQ, and CsrA emerged as global RBPs governing large posttranscriptional networks, either by facilitating the activities of basepairing sRNAs (Holmqvist et al, 2018; Santiago-Frangos & Woodson, 2018) or by acting as pleiotropic mRNA repressor (Potts et al, 2017), but little is known beyond. It remains largely unclear how sRNA-binding proteins are themselves regulated, how they are embedded in the protein–protein interaction network, and to which extent they cross-talk with transcriptional regulators
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
