Regulation of glmS expression in Escherichia coli: signaling within the hierarchically acting GlmYZ sRNA cascade is achieved by protein-sequestration

Two homologous sRNAs, GlmY and GlmZ, regulate the expression of key enzyme glucosamine-6-phosphate (GlcN6P) synthase (GlmS) in an hierarchical manner (1,2,3,4). GlmS catalyzes the key step in cell wall biosynthesis, the formation of the essential precursor GlcN6P. Base-pairing of unprocessed sRNA GlmZ with the glmS mRNA promotes GlmS synthesis. GlmZ is processed by RNase E and GlmZ:glmS base-pairing thereby abolished. Upon depletion of GlcN6P, GlmY accumulates and counteracts processing of GlmZ. This mechanism involves protein YhbJ that specifically binds GlmY and GlmZ. In yhbJ mutants, processing of GlmZ is abolished leading to constitutive activation of glmS. Here we address the mechanism of signal transduction within the sRNA cascade and the role of YhbJ. We hypothesize that both sRNAs compete for binding to YhbJ. Binding of GlmZ might lead to recruitment of RNase E and subsequent processing of GlmZ, whereas binding of GlmY sequesters protein YhbJ. Indeed, we observed specific interaction between RNase E and YhbJ. Furthermore, in vivo binding of GlmY and GlmZ by YhbJ seems to be dependent on GlcN6P levels. At sufficient levels of GlcN6P GlmZ is bound by YhbJ and processed by RNase E whereas GlmY is bound preferably upon GlcN6P-starvation. Thus, the GlmYZ regulatory cascade seems to be another system that involves modulation of protein activity by two sRNAs in order to control gene expression.