Administrative Supplement for Equipment Purchase

设备采购行政补充

基本信息

批准号：
10795516
负责人：
SEAN J JOHNSON
金额：
$ 8.16万
依托单位：
UTAH STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-10 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10795516
关键词：
Adaptor Signaling Protein Address Administrative Supplement Air Automobile Driving Biochemical Biological Assay Biomedical Research Biophysics Cell physiology Complex Data Deuterium Disease Feeds Future Genetic Transcription Hydrogen Malignant Neoplasms Mediating Medicine Molecular Molecular Conformation Monitor Mutagenesis Mutation Neurodegenerative Disorders Nuclear Nuclear RNA Pathway interactions Play Poly A Polyadenylation Polymerase Process Protein Dynamics Proteins RNA RNA Binding RNA Decay RNA Degradation RNA Helicase RNA Processing Regulation Research Personnel Role Structure Substrate Specificity System Technology biophysical techniques career equipment acquisition exosome experimental study genetic analysis helicase in vivo interest laser tweezer novel optic tweezer prevent protein complex recruit single molecule undergraduate student

项目摘要

Project Summary Nuclear RNA processing and surveillance is a complex process involving multiple proteins and protein assemblies that identify and eventually degrade targeted RNA substrates. The RNA helicase, Mtr4, plays a central role in this process by providing a bridge between substrate targeting and RNA decay by the RNA exosome. RNA recognition is performed directly by Mtr4 and by various adaptor proteins that recruit Mtr4 to targeted substrates. A major challenge is to understand the molecular details of how these proteins interact with RNA substrates and with each other to achieve substrate specificity. Additionally, accessory domains within Mtr4 play important but poorly defined roles in substrate recognition and processing. Notably, the available structural data demonstrate that Mtr4 is a highly dynamic protein, but it is not known how protein dynamics relate to helicase function. This project seeks to define the molecular basis for Mtr4 function by employing a variety of biochemical, biophysical and structural approaches, supported by in vivo genetic analyses. The specific aims of this project are to (1) describe the role of Mtr4 accessory domains and (2) characterize interactions within the TRAMP (Trf4-Air2-Mtr4) complex. Undergraduate and graduate researchers with interests in future careers in biomedical research or medicine will be involved in the project.

项目概要核RNA处理和监视是一个涉及多种蛋白质和蛋白质的复杂过程识别并最终降解目标 RNA 底物的组件。 RNA 解旋酶 Mtr4 发挥作用通过在底物靶向和RNA衰变之间架起一座桥梁，在这一过程中发挥着核心作用 RNA外泌体。 RNA 识别由 Mtr4 和各种招募的接头蛋白直接执行 Mtr4 到目标底物。一个主要的挑战是了解这些物质如何发挥作用的分子细节。蛋白质与 RNA 底物以及彼此之间相互作用以实现底物特异性。此外， Mtr4 内的辅助结构域在底物识别和加工。值得注意的是，现有的结构数据表明 Mtr4 是一种高度动态的蛋白质，但它目前尚不清楚蛋白质动力学与解旋酶功能有何关系。该项目旨在定义分子通过采用各种生物化学、生物物理和结构方法为 Mtr4 功能奠定基础，得到体内遗传分析的支持。该项目的具体目标是 (1) 描述 Mtr4 辅助结构域和 (2) 表征 TRAMP (Trf4-Air2-Mtr4) 复合物内的相互作用。对生物医学研究或未来职业感兴趣的本科生和研究生研究人员医学将参与该项目。