RNA Dynamics by Solution and Solid State Deuterium NMR

University Of Washington, Seattle WA

Investigators

Abstract

Title: Functional dynamics in microRNA precursors by NMR Ribonucleic acid (RNA) performs many essential functions in all living organisms. MicroRNAs are an important class of RNAs that regulate the vast majority of the human genome, however the molecular mechanism by which these microRNAs are produced from precursor species is unclear. The dynamic structure of the precursor species have implications on microRNA processing. The project investigates how intrinsic motional properties of the RNA and RNA-binding proteins regulate the biological pathways associated with RNA regulation of gene expression, as a paradigm to understanding the molecular logic of regulation. This research will be executed in a highly interdisciplinary manner, which will allow training of postdoctoral fellows and graduate students to interdisciplinary research at the interface of physics, chemistry and molecular biology. The project will involve under-represented minority students who will be included in the research activities. Material from the project will also be used in teaching at the graduate level and in specialized advanced undergraduate courses. The overarching goal of this project is to study the relationship between RNA motion and its biological function. The specific objective of the research is to understand how microRNAs are produced in a manner that is regulated in different cellular states. This project will investigate how RNA dynamics, intrinsic to RNA, is altered upon substrate binding and its effects on the efficiency of processing of microRNA precursors. Primarily solution and solid-state NMR will be used and advanced spectroscopic techniques will be developed. Experimental studies will be integrated into state-of-the-art computational modeling for atomistic level interpretation. Biochemical and cell-based experiments will also be performed to test the biological functional relevance of the project's discoveries. Spectroscopic tools developed within this project to study functional dynamics in RNA will be broadly applicable to other nucleic acid systems.This project is supported by Molecular and Cellular Biosciences Division in the Directorate for Biological Sciences.