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Small regulatory RNAs inhibit RNA polymerase II during the elongation phase of transcription

机译：小型调节性RNA在转录延长阶段抑制RNA聚合酶II

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摘要

Eukaryotic cells express a wide variety of endogenous small regulatory RNAs that regulate heterochromatin formation, developmental timing, defence against parasitic nucleic acids and genome rearrangement. Many small regulatory RNAs are thought to function in nuclei. For instance, in plants and fungi, short interfering RNA (siRNAs) associate with nascent transcripts and direct chromatin and/or DNA modifications. To understand further the biological roles of small regulatory RNAs, we conducted a genetic screen to identify factors required for RNA interference (RNAi) in Caenorhabditis elegans nuclei. Here we show that the gene nuclear RNAi defective-2 (nrde-2) encodes an evolu-tionarily conserved protein that is required for siRNA-mediated silencing in nuclei. NRDE-2 associates with the Argonaute protein NRDE-3 within nuclei and is recruited by NRDE-3/siRNA complexes to nascent transcripts that have been targeted by RNAi. We find that nuclear-localized siRNAs direct an NRDE-2-dependentrnsilencing of pre-messenger RNAs (pre-mRNAs) 3' to sites of RNAi, an NRDE-2-dependent accumulation of RNA polymerase (RNAP) II at genomic loci targeted by RNAi, and NRDE-2-dependent decreases in RNAP II occupancy and RNAP II transcriptional activity 3' to sites of RNAi. These results define NRDE-2 as a component of the nuclear RNAi machinery and demonstrate that metazoan siRNAs can silence nuclear-localized RNAs co-transcriptionally. In addition, these results establish a novel mode of RNAP II regulation: siRNA-directed recruitment of NRDE factors that inhibit RNAP II during the elongation phase of transcription.
机译：真核细胞表达多种内源性小调节RNA，它们调节异染色质的形成，发育时间，对寄生核酸的防御和基因组重排。人们认为许多小调节RNA在核中起作用。例如，在植物和真菌中，短干扰RNA（siRNA）与新生的转录本以及直接的染色质和/或DNA修饰相关。为了进一步了解小调节RNA的生物学作用，我们进行了基因筛选，以鉴定秀丽隐杆线虫核中RNA干扰（RNAi）所需的因素。在这里，我们显示了核RNAi缺陷2基因（nrde-2）编码的一种进化上保守的蛋白质，是siRNA介导的细胞核沉默所必需的。 NRDE-2与细胞核中的Argonaute蛋白质NRDE-3缔合，并被NRDE-3 / siRNA复合物募集到RNAi靶向的新生转录本上。我们发现核定位的siRNA指导信使前RNA（pre-mRNAs）3'的NRDE-2依赖性沉默沉默到RNAi的位点，RNA聚合酶（RNAP）II的NRDE-2依赖性积累在靶向的基因组位点。 RNAi和NRDE-2依赖的RNAi II占据和RNAi II的3'转录活性下降。这些结果将NRDE-2定义为核RNAi机制的组成部分，并证明后生动物siRNA可以使转录的核定RNA沉默。此外，这些结果建立了一种新型的RNAP II调控模式：siRNA指导的NRDE因子募集，该转录因子在转录延伸阶段抑制RNAP II。

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  • 来源
    《Nature》 |2010年第7301期|P.1097-1101|共5页
  • 作者

    Shouhong Guang; Aaron F. Bochner; Kirk B. Burkhart; Nick Burton; Derek M. Pavelec; Scott Kennedy;

  • 作者单位

    Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706, USA;

    Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706, USA;

    Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706, USA;

    Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706, USA;

    Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706, USA;

    Laboratory of Genetics, University of Wisconsin, Madison, Wisconsin 53706, USA Department of Pharmacology, University of Wisconsin, Madison, Wisconsin 53706, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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