Control of Transcription in Eukaryotic Cells

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定是针对RNA的 转录后的聚合酶已经启动。基因的表达必须 变化迅速的人经常被发现携带着一种RNA聚合酶，这种聚合酶启动了RNA 但合成很快就停止了，距离起始点不到50nT。其中 这些基因是许多原癌基因，如c-myc和c-fos，其 监管不当可能会对人类健康造成灾难性影响。这样做的目的是 研究是对RNA分子机制的更深层次的理解 聚合酶II建立和维持继续RNA链的能力 伸长率。这项工作要解决的问题包括： 它们伴随着转录的第一个阶段，这对 允许聚合酶逃避与启动子的相互作用？这是怎么回事 聚合酶随后锁定到稳定的转录-延伸状态？在……里面 特别是，RNA本身在控制后者方面扮演了什么角色 活动？RNA是否与聚合酶上的特定位点相互作用？ 在结合点的上游？能否识别模板序列 使RNA聚合酶从起始状态转变为 拉长状态特别难吗？

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?