RNA Dynamics by Solution and Solid State Deuterium NMR

标题：核磁共振在microRNA前体中的功能动力学核糖核酸（RNA）在所有生物体中执行许多基本功能。 microRNA是一类重要的RNA，调节绝大多数人类基因组，然而这些microRNA由前体物种产生的分子机制尚不清楚。前体物质的动态结构对microRNA加工有影响。 该项目研究RNA和RNA结合蛋白的内在运动特性如何调节与RNA调节基因表达相关的生物途径，作为理解调节分子逻辑的范式。这项研究将以高度跨学科的方式进行，这将使博士后研究员和研究生能够在物理，化学和分子生物学的界面上进行跨学科研究。该项目将涉及代表性不足的少数民族学生，他们将被纳入研究活动。该项目的材料也将用于研究生一级的教学和专门的高级本科课程。 该项目的首要目标是研究RNA运动与其生物学功能之间的关系。这项研究的具体目标是了解microRNA是如何以不同细胞状态下调节的方式产生的。该项目将研究RNA固有的RNA动力学如何在底物结合后改变，以及其对microRNA前体加工效率的影响。 将使用初级溶液和固态NMR，并将开发先进的光谱技术。实验研究将被集成到最先进的计算建模原子级的解释。还将进行生物化学和细胞实验，以测试该项目发现的生物功能相关性。本研究项目中开发的用于研究RNA功能动力学的光谱工具将广泛适用于其他核酸系统。本研究项目由生物科学理事会分子和细胞生物科学部支持。

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.