Research SummaryStructural mechanisms of RNA-mediated gene regulation in bacteria
Bacteria are adept at responding to environmental stresses and cues by precisely regulating different genes. Regulatory roles were traditionally attributed to proteins, however, it is now well established that RNAs plays a major role in genetic control. Discovery and deeper mechanistic insight into regulatory RNAs are both at very early stages. In pathogenic bacteria especially, the roles of regulatory RNAs are largely unknown. Understanding RNA-based regulation is central to understanding bacterial biology. My post-doctoral research has contributed towards understanding mechanisms of regulatory RNAs called riboswitches. Riboswitches directly sense metabolites to regulate related genes, often controlling growth, metabolism and stress-responses. I have also uncovered the mechanism of a widespread protein regulator called ANTAR and its target RNA, that together control key metabolic genes in some bacteria. In this proposal, I aim to understand i) how ANTAR and similar regulatory RNA-protein complexes function at the mechanistic and structural level, ii) how RNA-regulators control genetic responses to multiple, integrated signals and iii) mechanisms by which RNA-based regulatory complexes function in pathogenic bacteria. The overreaching goal of this proposal is to understand and ultimately target pathogenic bacteria. This will have substantial implications for human health
Figure Legend: RNAs respond to diverse cellular signals as well as to RNA-binding proteins to elicit control over genes in bacteria, ultimately affecting processes such as growth and metabolism, stress response and the ability to cause disease.