The molecular machinery of RNA metabolism and riboregulation in bacteria (360G-Wellcome-200873_Z_16_Z)

In response to stress conditions and environmental changes, bacteria generate scores of small RNAs that play key roles in reshaping the dynamic landscape of gene expression. This process involves chaperone proteins that facilitate the actions of such regulatory RNAs and enzymes that affect transcript lifetimes. We aim to understand the molecular basis of these processes. Trapped intermediates of the degradative machinery with bound regulatory RNAs and targeted substrates will be structurally characterised to visualize how transcripts are captured and channelled to active sites, where they meet a fate of rapid degradation or processing into matured forms. We will identify RNA targets of chaperones and the degradative machinery and explore whether the patterns change with physiological state or during the cell cycle, and why. We want to understand why the degradative machinery has a sub-cellular localization and the origins of its dynamic and cooperative interactions with substrates and the translational machinery. Our studies will help to explain how the use of RNA enables speed and accuracy to be attained in genetic regulation and enriches the capacity of even the simplest organisms to exhibit complex behaviour in homeostasis, development and pathogenesis. This knowledge could be exploited to treat threatening bacterial infections.