RNA聚合酶Ⅱ启动子近端暂停/释放的动态调控及生理作用研究进展

Dynamic Regulation and Physiological Role of Promoter-proximal Pause/Release of RNA PolymeraseⅡ:a Review

基因表达的精确时空调控对生物体的发育和生存至关重要。在多数后生动物中,RNA聚合酶Ⅱ(RNA polymeraseⅡ,RNAPⅡ)在发育和应激反应相关基因的启动子近端区域暂停,一旦受到环境或发育信号的刺激,RNAPⅡ从启动子近端向基因体(genebody)释放,进行有效延伸。RNAPⅡ在基因转录起始位点下游近端区域的暂停/释放是基因转录过程的必要环节,也是基因表达调控的关键步骤,与基因表达时空调控及多种人类疾病密切相关。综述了参与RNAPⅡ启动子近端暂停的维持和释放的调控机制的研究进展,重点探讨了其在机体发育的重要调控作用及其与其他基因调控机制的联系,并展望了RNAPⅡ启动子近端暂停与释放研究中的潜在问题和未来研究方向,以期为进一步解析RNAPⅡ启动子近端暂停与释放的调控机制及其在发育中的作用提供线索。

Precise temporal and spatial regulation of gene expression is important for the development and survival of organisms.In most metazoans,RNA polymeraseⅡ(RNAPⅡ)pauses in the promoter-proximal region of genes related to development and stress response.Once stimulated by environmental or developmental signals,RNAPⅡis released from the promoter to the gene body for effective extension.The promoter-proximal pausing/pause release of RNAPⅡat the downstream of transcriptional start site provides an important layer of regulation on RNAPⅡactivity in the promoter region and is closely related to spatial-temporal regulation of gene expression and a variety of human diseases.This paper aimed to review recent progress in studying the regula⁃tion mechanism of RNAPⅡpromoter-proximal pause,explored important roles of promoter-proximal pause/release of RNAPⅡin development and its potential relationship with other gene regulation mechanisms.This report also summarized the potential questions and research directions in this filed,in order to provide clues to clarify the molecular mechanism and roles of RNAPⅡpromoter-proximal pause/release in development.