DNA转录为RNA包括三个阶段:起始,延伸,终止,其中转录终止过程又可分为两步,RNA转录本的释放和DNA模板的释放。II型RNA聚合酶负责真核生物体内编码蛋白质的基因的转录,其转录终止也是蛋白质表达过程中的重要一步。
以往研究表明,聚合酶II终止转录过程必需RNA 3'端的多聚腺苷酸信号〔poly(A)〕, RNA前体的转录后剪切加工也和转录终止过程相关。另外,在β球蛋白基因的的3'侧还发现了专一性的转录终止信号。这说明聚合酶II转录终止过程涉及多种因素,但目前还不清楚这些因素间如何相互作用终止转录过程。
在最新研究中,来自英国的科学家用一种简单的核抽提液及自然的或人工合成的核酸模板监测到了哺乳动物RNA聚合酶的转录终止过程。结果表明,首先poly(A)位点的识别使转录终止成为可能,此后poly(A)位点被剪切,暴露出不受保护的RNA末端,导致结合在聚合酶II上的RNA转录本在核酸外切酶的作用下降解,该降解过程促使DNA模板和聚合酶II的脱离。而具有专一性终止信号的基因,如β球蛋白基因,则是在终止信号转录后被剪切,从而启动了RNA转录本的降解,致使DNA模板和聚合酶II脱离。而此终止过程也必须以poly(A)位点的识别为前提。
该研究成果作为封面论文发表于2008年3月14日的《分子细胞》(Molecular Cell)上。(科学网 穆宏平/编译)
生物谷推荐原始出处:
(Molecular Cell),Vol 29, 600-610, 14 March 2008,Steven West, Nicholas J. Proudfoot, and Michael J. Dye
Molecular Dissection of Mammalian RNA Polymerase II Transcriptional Termination
Steven West,1 Nicholas J. Proudfoot,1, and Michael J. Dye1,
1 Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, UK
Summary
Transcriptional termination of mammalian RNA polymerase II (Pol II) is an essential but little-understood step in protein-coding gene expression. Mechanistically, termination by all DNA-dependent RNA polymerases can be reduced to two steps, namely release of the RNA transcript and release of the DNA template. Using a simple nuclear fractionation procedure, we have monitored transcript and template release in the context of both natural and artificial Pol II terminator sequences. We describe the timing and relationship between these events and in so doing establish the roles of the poly(A) signal, cotranscriptional RNA cleavage events, and 5′-3′ exonucleolytic RNA degradation in the mammalian Pol II termination process.