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

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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.