RNA Polymerase II-Fctr Complexes in Transcription Cntrol

RNA 聚合酶 II-Fctr 复合物在转录控制中的作用

• 批准号: 6865305
• 负责人: JIANHUA FU
• 金额: $ 43.41万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6865305
• 关键词: DNA directed RNA polymerase; SDS polyacrylamide gel electrophoresis; Saccharomyces cerevisiae; X ray crystallography; chromatin; enzyme activity; enzyme complex; gene expression; genetic regulation; genetic transcription; messenger RNA; phosphoprotein phosphatase; phosphorylation; polymerase chain reaction; protein structure

DESCRIPTION (provided by applicant): Our long-term goal is to understand the structural basis for the regulation of RNA polymerase II Imachinery in the transcription cycle. The eukaryotic mRNA synthesis system has emerged as an enormous protein apparatus consisting of RNA polymerase II (Pol II) at its heart surrounded by layers of controlling factors. We recently cracked the phase problem for the 10-subunit Pol II (500 kDa) from yeast. This advent has made it feasible to unveil the apparatus in a more elaborate fashion, so we can analyze Pol II-factor(s) interactions that modulate the transcription activities of Pol I1. Transcription is the first step in gene expression. Signals from many cellular processes such as nutrient sensing, catabolite repression, hormone stimulation, differentiation and responses to environmental stimuli ultimately reach the level of transcription to exert their effects. Aberration of transcriptional control is one of the mechanisms underlying tumorigenesis, since cancer arises from disruption of the fine balance between proliferative and differentiative genetic programs. Oncogene products are frequently found to be key players in the control networks of signal transduction, cell cycle and transcription regulations. We propose to examine, in yeast, various Pol II-factor(s) complexes corresponding to distinct functional steps in the transcription cycle. Biochemical and X-ray crystallographic methods developed in the work of the 10-subunit Pol II and the ribosome will be employed, refined and extended to tackle this new generation of structural problems in transcription regulation. Specific aims for the project period are crystal structure determinations of three Pol II-factor complexes, including the pre-mRNA 5' capping enzyme, a Pol II specific phosphatase Fcpl and a subassembly of the Pol II transcription preinitiation complex.

描述（由申请人提供）：我们的长期目标是了解转录周期中RNA聚合酶II iPachinery的结构基础。真核mRNA合成系统已成为一种由RNA聚合酶II（POL II）组成的巨大蛋白质设备，其心脏周围是由控制因子层的层。最近，我们从酵母菌中解决了10毛Pol II（500 kDa）的相位问题。这次降临使以更精致的方式揭示设备的可行性，因此我们可以分析Pol II因子的相互作用，以调节POL I1的转录活动。转录是基因表达的第一步。来自许多细胞过程的信号，例如营养感应，分解代谢产物抑制，激素刺激，分化和对环境刺激的反应最终达到转录水平以发挥其作用。转录控制的像差是肿瘤发生的基本机制之一，因为癌症是由于增殖性和分化性遗传程序之间的良好平衡而引起的。癌基产品经常被认为是信号转导，细胞周期和转录法规的控制网络中的关键参与者。我们建议在酵母中检查各种Pol II因子复合物，对应于转录周期中不同的功能步骤。将在10-亚基pol II和核糖体的工作中开发的生化和X射线晶体学方法，将采用，完善和扩展，以解决转录调节中新一代的结构问题。在项目期间的具体目的是三个POL II因子复合物的晶体结构确定，包括前MRNA 5'上限酶，POL II特异性磷酸酶FCPL和POL II转录前启动络合物的子组装。