GlmY and GlmZ: A regulatory cascade composed of two small RNAs

在大肠杆菌中，中心代谢酶葡糖胺-6-磷酸（GlcN 6P）合酶GlmS的合成由两个同源sRNA组成的调节级联反馈调节。GlmS催化细胞壁生物合成所需的GlcN 6P的形成。降低的GlcN 6P浓度诱导sRNA GlmY的积累，这反过来抵消了第二sRNA GlmZ的加工。完全全长GlmZ与glmS转录物碱基配对并刺激GlmS合成。glmY的表达受双组分系统GlrR/GlrK控制，但GlcN 6P信号的感测发生在glmY转录后。在所提出的项目中，应解决三个问题：首先，应鉴定GlcN 6P传感机制。我们推测这一步可能涉及GlmY与蛋白YhbJ的结合。我们最近确定了GlmZ加工所需的YhbJ。其次，阐明GlmY和GlmZ之间的信号转导机制。我们的数据与模型一致，其中GlmY与YhbJ的结合触发GlmZ的加工，或者通过影响YhbJ与GlmZ加工酶的相互作用，或者通过控制因子的表达，该因子反过来控制该RNase的活性。对于后者，RNase E抑制蛋白RraB是一个很好的候选者，因为它的合成受GlcN 6P调节。最后，应识别GlrK/GlrR感知的信号。这将揭示GlmY除了控制GlmZ和glmS之外还具有的功能。

In Escherichia coli, synthesis of the central metabolic enzyme glucosamine-6-phosphate (GlcN6P) synthase GlmS is feedback-regulated by a regulatory cascade composed of two homologous sRNAs. GlmS catalyzes the formation of GlcN6P, which is required for biosynthesis of the cell wall. A decreasing GlcN6P concentration induces accumulation of sRNA GlmY, which in turn counteracts processing of the second sRNA, GlmZ. Exclusively full-length GlmZ base-pairs with the glmS transcript and stimulates GlmS synthesis. Expression of glmY is controlled by the two-component system GlrR/GlrK, but sensing of the GlcN6P signal takes place post glmY transcription. In the proposed project three questions shall be addressed: First, the GlcN6P sensing mechanism shall be identified. We speculate that this step might involve binding of GlmY by protein YhbJ. We recently identified YhbJ to be required for GlmZ processing. Second, the mechanism of signal transduction between GlmY and GlmZ shall be clarified. Our data are consistent with a model, in which binding of GlmY to YhbJ triggers processing of GlmZ, either by affecting the interaction of YhbJ with the GlmZ processing enzyme or by controlling expression of a factor that in turn controls activity of this RNase. For the latter, the RNase E inhibitory protein RraB is a good candidate, because its synthesis is regulated by GlcN6P. Finally, the signal sensed by GlrK/GlrR shall be identified. This will reveal functions that GlmY has in addition to the control of GlmZ and glmS.