Control of Transcription in Eukaryotic Cells

真核细胞转录的控制

• 批准号: 6626067
• 负责人: Donal Luse
• 金额: $ 32.56万
• 依托单位: CLEVELAND CLINIC FOUNDATION
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-07-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6626067
• 关键词: DNA directed RNA polymerase; HeLa cells; RNA biosynthesis; active sites; enzyme activity; eukaryote; gel mobility shift assay; gene expression; genetic promoter element; genetic regulation; genetic regulatory element; genetic transcription; nucleic acid hybridization; nucleic acid sequence; nucleic acid structure; polymerase chain reaction; stereochemistry; transcription factor

DESCRIPTION (provided by applicant): It is becoming increasingly clear that a significant fraction of gene regulatory decisions are directed at RNA polymerase after transcription has initiated. Genes whose expression must change quickly are often found to bear an RNA polymerase which has started RNA synthesis but halted shortly afterward, within 50 nt of the start point. Among these genes are many proto-oncogenes, such as c-myc and c-fos, whose misregulation can have catastrophic effects on human health. The goal of this research is a deeper understanding of the molecular mechanisms by which RNA polymerase II establishes and maintains competence to continue RNA chain elongation. Questions to be addressed by this work include: Among the events which accompany the very first stages of transcription, which are critical to allow polymerase to escape its interaction with the promoter? How does the polymerase subsequently lock into the stable transcript-elongation state? In particular, what role does the RNA itself play in controlling this latter event? Does the RNA interact with a specific site on the polymerase, well upstream of the point of bond formation? Can template sequences be identified which make the RNA polymerase's transition from the initiating to the elongating state particularly difficult?

描述（由申请人提供）： 越来越明显的是， 很大一部分基因调控决策是针对 RNA 转录开始后的聚合酶。其表达必须的基因 经常发现快速变化的RNA具有启动RNA的RNA聚合酶 合成但不久之后就停止了，在起始点的 50 nt 内。之中 这些基因是许多原癌基因，例如c-myc和c-fos，其 监管不当可能对人类健康造成灾难性影响。此举的目标 研究是对RNA分子机制的更深入理解 聚合酶 II 建立并维持延续 RNA 链的能力 伸长。这项工作要解决的问题包括： 它伴随着转录的最初阶段，这对于转录至关重要 让聚合酶逃避与启动子的相互作用？如何 聚合酶随后锁定稳定的转录延伸状态？在 特别是，RNA本身在控制后者方面发挥什么作用？ 事件？ RNA 是否与聚合酶上的特定位点相互作用？ 键形成点的上游？可以识别模板序列吗 使RNA聚合酶从起始酶转变为聚合酶 拉长状态特别困难？