权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Protein RNA Rearrangements in the Spliceosome

剪接体中蛋白质 RNA 重排

基本信息

批准号：
8586205
负责人：
CHARLES C QUERY
金额：
$ 3.53万
依托单位：
ALBERT EINSTEIN COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-08-01 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8586205
关键词：
3&apos Splice Site ATP phosphohydrolase Active Sites Affect Alternative Splicing Binding Binding Sites Bypass Catalysis Catalytic Domain Chemicals Chromatin Code Commit DNA Sequence Rearrangement Data Defect Development Elements Event Excision Fission Yeast Gene Expression Genetic Screening Genetic Transcription Goals Human Individual Infection Introns Investigation Joining Exons Ligands Link Mammalian Cell Mediating Modeling Modification Nucleotides Pathway interactions Pattern Polyadenylation Positioning Attribute Predisposition Process Proteins RNA RNA Splicing Reaction Rest Role Saccharomyces cerevisiae Series Site Small Nuclear RNA Spliceosome Assembly Pathway Spliceosomes Staging Structure Substrate Interaction System Techniques Testing Time U2 Small Nuclear Ribonucleoprotein U2 small nuclear RNA Yeasts genome-wide helicase improved in vivo mRNA Precursor novel research study single molecule tumorigenesis

项目摘要

DESCRIPTION (provided by applicant): Excision of introns from precursor messenger RNA by the spliceosome is a critical step in almost all human gene expression. This process is highly regulated, integrally linked with the transcription of genes and other processing events, such as polyadenylation and nucleotide modification. A better understanding of pre- mRNA splicing will be essential to further understand mechanisms that regulate splicing, that control patterns of alternative splicing, and that contribute to development, oncogenesis and retroviral infections. The mechanism by which the spliceosome recognizes the exact sites for the chemical events and how the reactions are catalyzed are not well understood. The long-term goals of this project are to understand interactions and rearrangements between spliceosome components and the RNA ligands that are substrates for the catalytic reactions. Ample evidence argues for multiple rearrangements of factors and multiple recognition events at the branch site. Investigation of these events - which are not understood mechanistically - will elucidate interactions and rearrangements among core components and may serve as a paradigm for rearrangements in the spliceosome and in other RNP machines. This proposal focuses on mechanisms by which altered spliceosomal dynamics impact splicing fidelity. Experiments will investigate contributions of the U1-U2 protein-interaction network and the ATPase Prp5 to intron definition and to the fidelity of spliceosome assembly. As the first ATP-dependent event, this step provides a unique commitment to spliceosome assembly and a simplified system for studying the action of a spliceosomal ATPase. Further experiments will focus on the binding site of the 3' splice site substrate for the second step of splicing, which will use an 'orthogonal spliceosome' system in yeast, and on the mechanism by which the second-step substrate replaces first-step product in the catalytic core. Finally, we are investigating the role of novel RNA-RNA interactions in the transition from the first-to-second step of splicing. Together, the models proposed in these aims will greatly improve our understanding of the dynamic range of RNA-RNA interactions at consecutive stages of splicing.

描述（由申请人提供）：