Exploring the Dynamic Structures of Nucleic Acids

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The increasing recognition of RNA’s importance provides strong motivation for understanding how its dynamic structures contribute to biology at the molecular scale. Much of RNA’s versatility is derived from its intrinsic conformational flexibility and capacity to interact with a broad range of cellular partners. Assessment of RNA’s structures is challenged by the variations that supports these multiple roles. This program supports the continued application of tightly coupled experimental and computational tools to characterize ensembles of RNA structures. Recent advances enhance the resolution or interpretation of solution-based measurements, revealing subtle but important changes in rigid elements, like duplexes, or the full range of structures assumed by highly flexible unpaired strands. This project now extends studies of RNA from isolated motifs to biologically functional elements and aims to resolve their atomically detailed workings. A distinct focus is on the structural variation of single-stranded motifs. The capture or release of these highly flexible regions is a potent signal exploited in regulating the translation of mRNAs into proteins, via interactions with ions, small ligands or RNA motifs such as duplexes or loops in helix-junction-helix motifs. Because of their importance in controlling gene expression, these motifs offer new targets for therapeutic intervention or strategies for stabilizing existing RNA-based drugs or vaccines. Finally, this project will continue successful efforts to characterize the interaction of flexible nucleic acid motifs with proteins, laying the groundwork for understanding how large nucleic acid-protein complexes function.