免疫应答中基因表达的转录延伸调控

摘要

基因转录是一个有序的多步骤过程,包括转录起始前、转录起始和转录延伸等几个阶段.长期以来,转录起始前及转录起始阶段调控一直被认为是基因转录的关键限速步骤.然而,近年来利用全基因组深度测序等新技术对转录过程的深入研究,发现转录起始后的转录延伸阶段也是许多基因表达调控的关键步骤,并且这种调控机制在从果蝇到哺乳动物的不同物种之间高度保守.本文综述了NELF、DSIF和P-TEFb等主要转录延伸调控因子调控RNA聚合酶Ⅱ转录暂停和高效转录延伸最新分子机制,并讨论了转录延伸调控在癌症、炎症以及病毒感染等疾病发生中的作用.%Transcription is a multi-stage process that coordinates several steps during the transcription cycle including pre-initiation,initiation and elongation.Recent advances by genome-wide study suggest that control of transcription elongation is a critical step for precise regulation of gene expression across species from Drosophila to mammals.Here we review the molecular mechanisms of how transcription elongation of RNA polymeraseⅡ(PolⅡ) is modulated by the major pausing factors-NELF,DSIF and the positive elongation factor P-TEFb,which is the key player in pause release.We also discuss the potential implications of regulation of transcription elongation in pathogenesis of cancer,inflammation and virus infection.