Hsu Lilian M
Program in Biochemistry, Mount Holyoke College, South Hadley, MA 01075, USA.
Biochim Biophys Acta. 2002 Sep 13;1577(2):191-207. doi: 10.1016/s0167-4781(02)00452-9.
Promoter escape is the last stage of transcription initiation when RNA polymerase, having initiated de novo phosphodiester bond synthesis, must begin to relinquish its hold on promoter DNA and advance to downstream regions (DSRs) of the template. In vitro, this process is marked by the release of high levels of abortive transcripts at most promoters, reflecting the high instability of initial transcribing complexes (ITCs) and indicative of the existence of barriers to the escape process. The high abortive initiation level is the result of the existence of unproductive ITCs that carry out repeated initiation and abortive release without escaping the promoter. The formation of unproductive ITCs is a widespread phenomenon, but it occurs to different extent on different promoters. Quantitative analysis of promoter mutations suggests that the extent and pattern of abortive initiation and promoter escape is determined by the sequence of promoter elements, both in the promoter recognition region (PRR) and the initial transcribed sequence (ITS). A general correlation has been found that the stronger the promoter DNA-polymerase interaction, the poorer the ability of RNA polymerase to escape the promoter. In gene regulation, promoter escape can be the rate-limiting step for transcription initiation. An increasing number of regulatory proteins are known to exert their control at this step. Examples are discussed with an emphasis on the diverse mechanisms involved. At the molecular level, the X-ray crystal structures of RNA polymerase and its various transcription complexes provide the framework for understanding the functional data on abortive initiation and promoter escape. Based on structural and biochemical evidence, a mechanism for abortive initiation and promoter escape is described.
启动子逃逸是转录起始的最后阶段，此时已从头起始磷酸二酯键合成的RNA聚合酶必须开始松开其对启动子DNA的结合，并向模板的下游区域（DSR）前进。在体外，这一过程的特征是大多数启动子处会释放大量流产转录本，这反映了初始转录复合物（ITC）的高度不稳定性，并表明逃逸过程存在障碍。高流产起始水平是由于存在非生产性ITC，这些ITC进行重复起始和流产释放而不逃离启动子。非生产性ITC的形成是一种普遍现象，但在不同启动子上的发生程度不同。对启动子突变的定量分析表明，流产起始和启动子逃逸的程度和模式由启动子元件的序列决定，这些元件位于启动子识别区域（PRR）和初始转录序列（ITS）中。已发现一种普遍的相关性，即启动子DNA-聚合酶相互作用越强，RNA聚合酶逃离启动子的能力越差。在基因调控中，启动子逃逸可能是转录起始的限速步骤。已知越来越多的调控蛋白在此步骤发挥控制作用。文中讨论了相关例子，并重点强调了其中涉及的多种机制。在分子水平上，RNA聚合酶及其各种转录复合物的X射线晶体结构为理解流产起始和启动子逃逸的功能数据提供了框架。基于结构和生化证据，描述了一种流产起始和启动子逃逸的机制。
