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.

项目概要/摘要 RNA 聚合酶延伸和终止的控制尚不完全清楚。在这项工作中，我们将研究 C 端结构域磷酸酶 Rtr1 和 Ssu72 在 RNA 调节中的作用聚合酶 II (RNAPII) 延伸和终止。我们的初步研究结果表明，Rtr1 的删除导致转录延伸过程中 RNAPII 提前终止效率的整体变化。先前的工作表明，Ssu72 功能的破坏会导致 RNAPII 终止减少，从而导致终结符通读缺陷。在本提案中，我们将测试每种磷酸酶的扰动如何影响转录延伸和终止。此外，我们将对 Rtr1 和 Ssu72 底物特异性可进一步表征其作用机制。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定位唯一和/或重叠的目标 RNAPII C 末端结构域内的位点。总的来说，这些研究将揭示基本过程 RNAPII 转录控制在人类多种疾病状态下被破坏。