In the past year, we have made progress in the subject of selective cation binding by RNA and how this can regulate gene expression. Through a combination of biophysical, biochemical and crystallographic analyses, we have determined how a bacterial gene-regulatory RNA (riboswitch), which was shown to bind to Mn(II) by our collaborators in the Storz laboratory at NICHD can also bind with high affinity to Cd(II) and control gene expression. We discovered that this RNA exploits the unusual ability of these two ions to adopt a heptacoordinated geometry to distinguish them from the majority of other metal ions (that are typically hexacoordinated). This insight could drive the design of biosensors, as well as potential detoxyfying agents. In collaboration with the Balasubramanian and Myong laboratories (Cambridge University and Johns Hopkins University, respectively) we have also made an important advance in understanding the molecular mechanism of the DEAH family of helicases, widespread and essential proteins that remodel cellular RNAs and RNPs. Our structural and single-molecule characterization of DHX36, an essential helicase involved in control of gene expression, the stress response, and cardiovascular development, revealed how these enzymes can use the energy of binding to the nucleic acid substrate alone to perform mechanical work. DHX36 is notable for its high specificity for G-quadruplex containing nucleic acids, and our structural analysis is also the first to show how the cellular machinery can recognize and remodel this important type of DNA and RNA structures.
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