Control of Transcription in Eukaryotic Cells

描述（由申请人提供）：越来越清楚的是， 很大一部分基因调控决定是针对RNA的 在转录开始后聚合酶。基因的表达必须 通常发现快速变化的RNA携带RNA聚合酶， 合成，但不久之后在起始点的50 nt内停止。之间 这些基因是许多原癌基因，如c-myc和c-fos， 监管不当可能对人类健康造成灾难性影响。这个目标 研究是对RNA分子机制的更深入理解， 聚合酶II建立并维持RNA链的延续能力 伸长率这项工作要解决的问题包括： 伴随着转录的最初阶段，这对 让聚合酶逃脱与启动子的相互作用如何 聚合酶随后锁定到稳定的转录延长状态？在 特别是，RNA本身在控制后者中起什么作用 事件？RNA是否与聚合酶上的特定位点相互作用 在键形成点的上游模板序列能被识别吗 使RNA聚合酶从起始转变为 拉伸状态特别困难？

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?