Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Mol Cell. 2012 May 11;46(3):311-24. doi: 10.1016/j.molcel.2012.03.006. Epub 2012 Apr 5.
We report a function of human mRNA decapping factors in control of transcription by RNA polymerase II. Decapping proteins Edc3, Dcp1a, and Dcp2 and the termination factor TTF2 coimmunoprecipitate with Xrn2, the nuclear 5'-3' exonuclease "torpedo" that facilitates transcription termination at the 3' ends of genes. Dcp1a, Xrn2, and TTF2 localize near transcription start sites (TSSs) by ChIP-seq. At genes with 5' peaks of paused pol II, knockdown of decapping or termination factors Xrn2 and TTF2 shifted polymerase away from the TSS toward upstream and downstream distal positions. This redistribution of pol II is similar in magnitude to that caused by depletion of the elongation factor Spt5. We propose that coupled decapping of nascent transcripts and premature termination by the "torpedo" mechanism is a widespread mechanism that limits bidirectional pol II elongation. Regulated cotranscriptional decapping near promoter-proximal pause sites followed by premature termination could control productive pol II elongation.
我们报告了人类 mRNA 去帽因子在控制 RNA 聚合酶 II 转录中的作用。去帽蛋白 Edc3、Dcp1a 和 Dcp2 以及终止因子 TTF2 与核 5'-3'外切酶 Xrn2 共免疫沉淀，Xrn2 是一种“鱼雷”，可促进基因 3' 末端的转录终止。通过 ChIP-seq，Dcp1a、Xrn2 和 TTF2 定位于转录起始位点 (TSS) 附近。在具有 5' 暂停 pol II 峰的基因中，去帽或终止因子 Xrn2 和 TTF2 的敲低将聚合酶从 TSS 转移到上游和下游远端位置。这种 pol II 的重新分布在幅度上与伸长因子 Spt5 耗竭引起的分布相似。我们提出，通过“鱼雷”机制偶联新生转录本的去帽和过早终止是限制双向 pol II 延伸的广泛机制。在启动子近端暂停位点附近进行受调控的共转录去帽，随后过早终止，可能控制有效的 pol II 延伸。
