Structural and functional studies of RNase MRP RNP

RNase MRP RNP 的结构和功能研究

基本信息

批准号：
10439791
负责人：
ANDREY S. KRASILNIKOV
金额：
$ 34.37万
依托单位：
PENNSYLVANIA STATE UNIVERSITY, THE
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-16 至 2024-07-31
项目状态：
已结题

项目摘要

Project Summary This project is focused on structural and functional studies of Ribonuclease (RNase) MRP. RNase MRP an essential and universal site-specific eukaryotic endoribonuclease. It is a 450 kDa multicomponent catalytic ribonucleoprotein (RNP) related to RNase P, but it has evolved to have a distinct substrate specificity and unique cellular functions. RNase MRP is involved in the metabolism of a wide range of RNA molecules, including rRNA and some mRNAs. In humans, altered RNase MRP activity results in a range of developmental disorders that typically lead to an extremely short stature, brittle hair, predisposition to cancers, and other abnormalities; the mechanisms causing these problems are not known as RNase MRP remains understudied. The specific aims of the proposal are: 1. Determination of the structural organizations of the S. cerevisiae RNase MRP holoenzyme using cryo- electron microscopy (cryo-EM). 2. Characterization of interactions of yeast RNase MRP with its substrates. This proposal will reveal the structure of RNase MRP and its divergence from its RNase P progenitor. It will uncover the respective roles of RNase MRP RNA and proteins in the interactions with a diverse range of substrates and clarify the mechanisms of RNase MRP substrate recognition and cleavage site selection, paving the way to the characterization of RNase MRP cellular functions. These studies will have a broad impact beyond the RNase MRP/P field by revealing the interplay of proteins and RNA in one of the most complex RNP enzymes, and by advancing our understanding of the structure, function, and evolution of catalytic RNPs.

项目摘要该项目的重点是核糖核酸酶（RNase）MRP的结构和功能研究。 RNASE MRP AN 必需的和普遍的特定地点真核内核切酶。它是450 kDa多组分催化与RNase P相关的核糖核蛋白（RNP），但已演变为具有独特的底物特异性和独特的蜂窝函数。 RNase MRP参与了广泛的RNA分子的代谢，包括rRNA和一些mRNA。在人类中，RNase MRP活性改变导致一定范围发育障碍通常导致身材极短，头发脆弱，倾向癌症和其他异常；引起这些问题的机制不称为RNase MRP 仍在研究。该提案的具体目的是： 1。使用冷冻的酿酒酵母MRP Holoenzyme的结构组织确定电子显微镜（冷冻EM）。 2。表征酵母RNase MRP与其底物的相互作用。该提案将揭示RNase MRP的结构及其与RNase P祖细胞的差异。会发现RNase MRP RNA和蛋白质在与多种范围的相互作用中的各自作用底物并阐明RNase MRP底物识别和切割位点选择的机制，为RNase MRP细胞功能的表征铺平了道路。这些研究将有广泛的通过揭示蛋白质和RNA的相互作用，超出RNase MRP/P场的影响最多。复杂的RNP酶，并通过促进我们对结构，功能和演变的理解催化RNP。