Structural and functional studies of RNase MRP RNP

RNase MRP RNP 的结构和功能研究

• 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
• 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
• 来源: https://reporter.nih.gov/project-details/10439791
• 关键词: 3-Dimensional; Address; Biochemical; Catalysis; Catalytic Domain; Catalytic RNA; Cell Cycle; Cell physiology; Cells; Complex; Cryoelectron Microscopy; Defect; Development; Disease; Endoribonucleases; Enzymes; Equipment; Eukaryota; Eukaryotic Cell; Evolution; Hair; Health; Holoenzymes; Human; Knowledge; Lead; Location; Malignant Neoplasms; Messenger RNA; Metabolism; Nuclear; Play; Positioning Attribute; Predisposition; Proteins; RNA; RNA Folding; RNAse MRP; RNase P; Reagent; Regulation; Resolution; Ribonucleoproteins; Ribosomal RNA; Role; Saccharomyces cerevisiae; Site; Specific qualifier value; Structure; Substrate Specificity; U2 small nuclear RNA; Yeasts; catalyst; developmental disease; experience; organizational structure; progenitor; reconstruction

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.

项目总结

项目成果

Proteins Rpr2 and Pop3 increase the activity and thermal stability of yeast RNase P.

• DOI: 10.1080/15476286.2023.2201110
• 发表时间: 2023-01
• 期刊: RNA BIOLOGY
• 影响因子: 4.1
• 作者: Perederina, Anna;Berezin, Igor;Krasilnikov, Andrey S.
• 通讯作者: Krasilnikov, Andrey S.