Laboratoires de Virologie Moléculaire, Institut de Génétique Humaine, CNRS UPR1142, 34396 Montpellier, France.
Cell. 2012 Sep 14;150(6):1147-57. doi: 10.1016/j.cell.2012.08.004.
Transcription elongation is increasingly recognized as an important mechanism of gene regulation. Here, we show that microprocessor controls gene expression in an RNAi-independent manner. Microprocessor orchestrates the recruitment of termination factors Setx and Xrn2, and the 3'-5' exoribonuclease, Rrp6, to initiate RNAPII pausing and premature termination at the HIV-1 promoter through cleavage of the stem-loop RNA, TAR. Rrp6 further processes the cleavage product, which generates a small RNA that is required to mediate potent transcriptional repression and chromatin remodeling at the HIV-1 promoter. Using chromatin immunoprecipitation coupled to high-throughput sequencing (ChIP-seq), we identified cellular gene targets whose transcription is modulated by microprocessor. Our study reveals RNAPII pausing and premature termination mediated by the co-operative activity of ribonucleases, Drosha/Dgcr8, Xrn2, and Rrp6, as a regulatory mechanism of RNAPII-dependent transcription elongation.
转录延伸越来越被认为是基因调控的一个重要机制。在这里，我们表明微处理器以 RNAi 独立的方式控制基因表达。微处理器协调终止因子 Setx 和 Xrn2 的募集，以及 3'-5'外切核酸酶 Rrp6，通过切割茎环 RNA TAR，在 HIV-1 启动子处启动 RNAPII 暂停和过早终止。Rrp6 进一步处理切割产物，产生一种小 RNA，该小 RNA是介导 HIV-1 启动子上有效转录抑制和染色质重塑所必需的。使用与高通量测序相结合的染色质免疫沉淀（ChIP-seq），我们鉴定了受微处理器调节的细胞基因靶标。我们的研究揭示了由核糖核酸酶 Drosha/Dgcr8、Xrn2 和 Rrp6 的协同活性介导的 RNAPII 暂停和过早终止，作为 RNAPII 依赖性转录延伸的一种调节机制。
