Khan Muna A, Görke Boris
Department of Microbiology, Immunobiology and Genetics, Max Perutz Labs, University of Vienna, Vienna Biocenter (VBC), 1030 Vienna, Austria.
Microb Cell. 2020 Apr 15;7(5):139-142. doi: 10.15698/mic2020.05.717.
Synthesis of glucosamine-6-phosphate (GlcN6P) by the enzyme GlmS initiates bacterial cell envelope biosynthesis. To ensure ongoing synthesis, GlcN6P homeostasis is required. achieves this through a post-transcriptional control mechanism comprising the RNA-binding protein RapZ and small RNAs (sRNAs) GlmY and GlmZ. GlmZ stimulates translation by base-pairing. When GlcN6P is abundant, GlmZ is cleaved and inactivated by endoribonuclease RNase E. Cleavage depends on RapZ, which binds GlmZ and recruits RNase E. Decreasing GlcN6P concentrations provoke up-regulation of the decoy sRNA GlmY which sequesters RapZ, thereby suppressing GlmZ decay. In our current study we identify RapZ as the GlcN6P sensor. GlcN6P-free RapZ interacts with and stimulates phosphorylation of the two-component system (TCS) QseE/QseF triggering expression. Thereby generated GlmY sequesters RapZ into stable complexes, allowing for expression. Sequestration by GlmY also disables RapZ to stimulate QseE/QseF, providing a negative feed-back loop limiting the response. When GlcN6P is replenished, GlmY is released from RapZ and rapidly degraded. Our work has revealed a complex regulatory scenario, in which an RNA binding protein senses a metabolite and communicates with two sRNAs, a TCS and ribonuclease RNase E to achieve metabolite homeostasis.
由GlmS酶合成的6-磷酸葡萄糖胺（GlcN6P）启动细菌细胞壁生物合成。为确保持续合成，需要维持GlcN6P的稳态。这是通过一种转录后控制机制实现的，该机制包括RNA结合蛋白RapZ以及小RNA（sRNA）GlmY和GlmZ。GlmZ通过碱基配对刺激翻译。当GlcN6P丰富时，GlmZ被核糖核酸内切酶RNase E切割并失活。切割依赖于RapZ，RapZ结合GlmZ并募集RNase E。GlcN6P浓度降低会引发诱饵sRNA GlmY的上调，GlmY会隔离RapZ，从而抑制GlmZ的降解。在我们当前的研究中，我们确定RapZ为GlcN6P传感器。无GlcN6P的RapZ与双组分系统（TCS）QseE/QseF相互作用并刺激其磷酸化，从而触发表达。由此产生的GlmY将RapZ隔离到稳定的复合物中，从而允许表达。GlmY的隔离也使RapZ无法刺激QseE/QseF，从而提供一个负反馈环来限制反应。当补充GlcN6P时，GlmY从RapZ释放并迅速降解。我们的工作揭示了一种复杂的调控情况，即一种RNA结合蛋白感知一种代谢物，并与两种sRNA、一种TCS和核糖核酸酶RNase E进行通信，以实现代谢物稳态。
