Regulation of RNA Polymerase II transcription by the phosphatase Rtr1

磷酸酶 Rtr1 对 RNA 聚合酶 II 转录的调节

基本信息

批准号：
9920013
负责人：
AMBER L. MOSLEY
金额：
$ 36.28万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-01 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9920013
关键词：
4-thiouracil Affinity Chromatography Binding C-terminal Cells Code Complementary RNA Complex Coupled DNA Repair DNA-Directed RNA Polymerase Data Defect Disease Eukaryota Eukaryotic Cell Excision Genes Genetic Genetic Screening Genetic Transcription Global Change Goals Human Hydrolysis Laboratories Lead Light Maintenance Mass Spectrum Analysis Measures Messenger RNA Molecular Mutation Pathway interactions Phenotype Phosphoric Monoester Hydrolases Phosphorylation Phosphorylation Site Play Process Proteins Proteomics RNA RNA Decay RNA Degradation RNA Polymerase II RNA Processing Regulation Regulatory Pathway Role Saccharomyces cerevisiae Serine Shapes Site Small Nucleolar RNA Substrate Specificity Testing Transcript Transcription Elongation Transcription Process Transcriptional Regulation Tyrosine Untranslated RNA Work Yeasts chromatin modification experimental study fitness genome-wide analysis histone modification in vivo mRNA Cleavage and Polyadenylation Factors mutant phosphoproteomics protein expression recruit transcription termination transcriptome

项目摘要

Project Summary/Abstract The control of RNA Polymerase elongation and termination is not fully understood. In this work, we will investigate the role of the C-terminal domain phosphatases Rtr1 and Ssu72 in the regulation of RNA Polymerase II (RNAPII) elongation and termination. Our preliminary findings suggest that deletion of Rtr1 results in global changes in the efficiency of early termination of RNAPII during transcription elongation. Previous work has shown that disruption of Ssu72 function leads to decreased RNAPII termination resulting in terminator read-through defects. In this proposal, we will test how perturbations of each phosphatase effect transcription elongation and termination. Additionally, we will perform enzymatic characterization of Rtr1 and Ssu72 substrate specificity to further characterize their mechanisms of action. Finally, we will determine the degree of interplay between Rtr1 and Ssu72 to determine if they are able to target unique and/or overlapping sites within the RNAPII C-termination domain. Overall, these studies will shed light on the fundamental process of RNAPII transcription control which is disrupted in numerous disease states in humans.

项目摘要/摘要 RNA聚合酶伸长和终止的控制尚不完全了解。在这项工作中，我们将研究C末端结构域磷酸酶RTR1和SSU72在RNA调节中的作用聚合酶II（RNAPII）伸长和终止。我们的初步发现表明RTR1的删除结果导致转录伸长期间RNAPII早期终止效率的全球变化。先前的工作表明，SSU72功能的中断导致RNAPII终止降低，导致终结者读取缺陷。在此提案中，我们将测试每种磷酸酶效应的扰动转录伸长和终止。此外，我们将对RTR1和 SSU72底物特异性以进一步表征其作用机理。最后，我们将确定 RTR1和SSU72之间的相互作用程度，以确定它们是否能够靶向独特和/或重叠 RNAPII C终止域内的站点。总体而言，这些研究将阐明基本过程 RNAPII转录控制在人类中许多疾病状态中受到破坏。