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

肠道细菌在它们的自然栖息地——人类消化道中会遇到各种各样的外部pH值。这些细菌通过选择性表达多种应激蛋白（包括氧化还原调节剂、转运蛋白、伴侣蛋白以及质周蛋白和包膜蛋白）来响应pH值的变化。这些蛋白谱变化背后的pH稳态机制尚不清楚。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显示出一种新的调节机制，即pH值影响RNA折叠动力学，从而影响顺式下游基因的表达。值得注意的是，我们的新研究表明，这种独特的核糖体调节剂也可以作为小RNA影响反式编码基因。本项目旨在全面了解这种pH响应RNA元件控制其多种体内靶标表达的分子机制，以及这种核糖开关/sRNA调节器在响应自然pH波动时影响的生理网络。我们的研究特别有趣，因为它可能确定超出单个细菌物种的功能和调节原理。

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.