INVESTIGATING THE PROPOSED 'SWITCHING' MECHANISM OF VARIOUS RIBOSWITCHES

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Riboswitches are structured mRNA elements found predominantly in bacteria. Upon recognition of specific cellular metabolies these RNAs are directly responsible for regulating gene expression at both the transcriptional and translational levels. Because riboswitches are found predominantly in bacteria and represent potential novel drug targets, these RNAs have been of recent interest for structure-function relationships. A metabolite-induced conformational change is a central part of the proposed mechanism of riboswitch function. Our research has focused on the nature of the structural changes elicited by metabolite-binding. Much discussion in the literature has debated whether ligand recognition results in global changes in the RNA or simply local rearrangements around the binding pocket. Our research at the BioCAT beamline demonstrates that different riboswitches behave idiosyncratically, perhaps indicating that the conformational changes are tuned to the genetic context of each riboswitch. Additionally, our work at BioCAT has allowed direct observation of the metabolite-bound and metabolite-free conformation of a riboswitch that recognizes the second messenger cyclic diguanylate. This is the first riboswitch reported which recongizes a second messenger and is responsible for regulating a wide variety of genes involved in signaling instead of the more common riboswitch targets relating