Chemical and Bio-enzymatic nucleotide labeling for RNA Structure and Dynamics

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With this award, the Chemistry of Life Processes program is funding the research of Professor T. Kwaku Dayie of the University of Maryland at College Park to examine the structural and dynamic basis of RNA regulation. RNAs are involved in many critical processes in the cell that range from sensing chemicals, speeding up chemical reactions, to controlling virus infections. Yet even though in humans more than 98% of the DNA is used up for making RNA and less than 2% for making proteins, more than 95% of the structures contained in the Protein Data Bank, a repository of 3D structures of biological molecules, belong to proteins and less than 2% of the structures belong to RNAs. This huge disparity stems from the properties of RNAs that make it harder to determine the structures of the RNAs. Professor Dayie develops new methods for the determination of the RNA structure and fill in this critical knowledge gap. These new strategies make RNA more amenable for structural and dynamic studies and facilitate biotechnology applications. The new reagents generated by the research are made available to the community of scientists who study the structure of RNA, including those from industry and from outside USA. Professor Dayie contributes to an outreach program that introduces high school, undergraduate, and graduate students to methods for the study of the structure of RNA and helps them understand how RNA controls signaling in cells. The proposed studies provide critical and new solid phase labeling technologies that can enable the filling of a major gap in RNA structural biology, namely the paucity of RNA structures in PDB. These structures can be used to decipher the molecular basis for the dynamic regulation of gene expression by RNA, which is still poorly understood. Dr. Dayie combines high resolution NMR spectroscopy and small angle x-ray scattering (SAXS) with chemical labeling technologies to study the dynamic basis of RNA signaling. Information from this study provides new insights into biological ligand-induced RNA binding/cell signaling.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.