RNA Dynamics by Solution and Solid State Deuterium NMR

标题：通过 NMR 检测 microRNA 前体的功能动力学 核糖核酸 (RNA) 在所有生物体中发挥着许多重要功能。 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。前体物种的动态结构对 microRNA 加工有影响。 该项目研究了 RNA 和 RNA 结合蛋白的内在运动特性如何调节与 RNA 基因表达调节相关的生物途径，作为理解调节分子逻辑的范例。这项研究将以高度跨学科的方式进行，这将允许博士后研究员和研究生接受物理、化学和分子生物学交叉学科研究的培训。该项目将涉及代表性不足的少数族裔学生，他们将被纳入研究活动。该项目的材料还将用于研究生教学和专业高级本科课程。 该项目的总体目标是研究 RNA 运动与其生物学功能之间的关系。该研究的具体目标是了解 microRNA 是如何以在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时发生改变及其对 microRNA 前体加工效率的影响。 将主要使用溶液和固态核磁共振，并开发先进的光谱技术。实验研究将被整合到最先进的计算模型中，以进行原子级解释。还将进行生化和细胞实验，以测试该项目发现的生物功能相关性。该项目开发的用于研究 RNA 功能动力学的光谱工具将广泛适用于其他核酸系统。该项目得到生物科学理事会分子和细胞生物科学部的支持。

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.