Cis and trans control of genes by a pH-responsive 5´ UTR

肠道细菌在其自然栖息地--人类消化道中遇到广泛的外部pH值。这些细菌通过选择性表达许多应激蛋白（包括氧化还原调节剂、转运蛋白、伴侣蛋白以及周质和包膜蛋白）来响应pH变化。这些蛋白质谱变化背后的pH稳态机制仍不清楚。我们最近描述了第一个pH响应RNA元件（PRE）。这种以前未表征的RNA表现出一种新的调节机制，即pH影响RNA折叠动力学，从而影响其下游基因的顺式表达。值得注意的是，我们的新研究表明，这种独特的核糖核酸调节因子也可以作为小RNA影响反式编码基因。本项目的目的是实现一个彻底的理解的分子机制，通过这种pH响应RNA元件控制其不同的体内目标的表达，和生理网络的影响，这种核糖开关/sRNA调节器在响应自然pH值的波动。我们的研究特别有趣，因为它可以确定超越单个细菌物种的功能和调控原则。

Enteric bacteria encounter a wide range of external pH in their natural habitat, the human digestive tract. These bacteria respond to pH changes by selective expression of numerous stress proteins including redox modulators, transporters, chaperons, as well as periplasmic and envelope proteins. The mechanisms of pH homeostasis underlying these protein profile changes remain unclear. We recently described the first pH-responsive RNA element (PRE). This previously uncharacterized RNA exhibits a novel regulatory mechanism whereby pH influences RNA folding dynamics to affect expression of its downstream gene in cis. Remarkably, our new studies demonstrate that this unique riboregulator also acts as a small RNA to affect trans-encoded genes. The present project aims to achieve a thorough understanding of the molecular mechanisms by which this pH responsive RNA element controls expression of its diverse in vivo targets, and of the physiological network influenced by this riboswitch/sRNA regulator in response to natural pH fluctuations. Our study is particularly interesting as it may identify functions and regulatory principles that extend beyond individual bacterial species.