Bacterial RNA thermometers: From individual examples to global analyses

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Structured RNA regions influence every step in the gene expression program. Many bacterial heat shock and virulence genes are regulated by RNA thermometers (RNATs), which are molecular zippers that control translation initiation. They adopt a structure that blocks the ribosome binding site at low temperatures. A temperature upshift to 37°C (virulence genes) or higher (heat shock genes) destabilizes the structure and permits translation.In the previous funding period, we have studied various natural and synthetic RNATs in molecular detail. By using a combination of in vitro structure probing and next-generation sequencing we mapped the entire RNA structurome of the human pathogen Yersinia pseudotuberculosis at three different temperatures. We now want to take advantage of this comprehensive data resource and characterize two distinct types of regulation. (i) Following the initial characterization of more than 25 novel RNATs, the structure and physiological function of a number of these regulatory elements will be evaluated. We are particularly interested in the virulence factor CnfY, and components of the oxidative stress response and type III secretion system. (ii) The RNA structurome results suggest a regulatory concept, in which several small regulatory RNAs undergo temperature-dependent conformational changes that mask or unmask their target interaction region. We will further evaluate this observation and study its effect on target gene regulation. In a third work package, we plan to capitalize on a previously developed in vivo RNA structuromics approach with the goal to learn how RNAs fold in the living cell.