In the past year, we have made further progress in elucidating the mechanism DHX36, a member of the DEAH family of helicases that has a unique substrate specificity for G-quadruplex nucleic acids, and whose loss results in fatal disruption of hematopoiesis. In collaboration with Professor Myong (Johns Hopkins University) we have demonstrated that this enzyme interacts differently with DNA and RNA G-quadruplexes, and that the interactions of the core of the helicase are responsible for the mechanistic divergence. We have also participated in the development of cutting-edge methods for biophysical analysis of RNA. In collaboration with Professor Markelz (The University at Buffalo) we have shown the feasibility of employing terahertz spectroscopy on crystalline RNA samples directly to measure dynamical properties of the hydrated nucleic acid. In collaboration with Professor Woodson (Johns Hopkins University) we have extended the single-molecule vectorial folding assay to the real-time analysis of folding of regulatory RNAs. In collaboration with Dr. Yun-Xing Wang (NCI), we have employed the ultrabright, pulsed radiation from the X-ray free-electron laser to determine the structure of a bacterial alarmone-sensing RNA.
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