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QiRNA is a new type of small interfering RNA induced by DNA damage

机译：QiRNA是DNA损伤诱导的新型小干扰RNA

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摘要

RNA interference pathways use small RNAs to mediate gene silencing in eukaryotes. In addition to small interfering RNAs (siRNAs) and microRNAs, several types of endogenously produced small RNAs have important roles in gene regulation, germ cell maintenance and transposon silencing. The production of some of these RNAs requires the synthesis of aberrant RNAs (aRNAs) or pre-siRNAs, which are specifically recognized by RNA-dependent RNA polymerases to make double-stranded RNA. The mechanism for aRNA synthesis and recognition is largely unknown. Here we show that DNA damage induces the expression of the Argonaute, protein QDE-2 and a new class of small RNAs in the filamentous fungus Neurospora crassa. This class of small RNAs, known as qiRNAs because of their interaction with QDE-2, are about 20-21 nucleotides long (several nudeotides shorter than Neurospora siRNAs), with a strong preference for uridine at the 5' end, and originate mostly from the ribosomal DNA locus. The production of qiRNAs requires the RNA-dependent RNA polymerase QDE-1, the Werner and Bloom RecQ DNA helicase homologue QDE-3 and dicers. qiRNA biogenesis also requires DNA-damage-induced aRNAs as precursors, a process that is dependent on both QDE-1 and QDE-3. Notably, our results suggest that QDE-1 is the DNA-dependent RNA polymerase that produces aRNAs. Furthermore, the Neurospora RNA interference mutants show increased sensitivity to DNA damage, suggesting a role for qiRNAs in the DNA-damage response by inhibiting protein translation.
机译：RNA干扰途径使用小RNA介导真核生物中的基因沉默。除了小干扰RNA（siRNA）和microRNA，内源性产生的几种小RNA在基因调节，生殖细胞维持和转座子沉默中也起着重要作用。这些RNA中的某些RNA的产生需要合成异常的RNA（aRNA）或pre-siRNA，它们会被依赖于RNA的RNA聚合酶特异性识别以生成双链RNA。 aRNA合成和识别的机制很大程度上未知。在这里，我们显示DNA损伤诱导丝状真菌Neurospora crassa中的Argonaute，蛋白QDE-2和一类新的小RNA的表达。这类小RNA由于与QDE-2相互作用而被称为qiRNA，长约20-21个核苷酸（比Neurospora siRNA短几个核苷酸），在5'端强烈偏好尿苷，并且主要来源于核糖体DNA基因座。 qiRNA的生产需要RNA依赖的RNA聚合酶QDE-1，Werner和Bloom RecQ DNA解旋酶同系物QDE-3和二聚体。 qiRNA生物发生还需要DNA损伤诱导的aRNA作为前体，这一过程既取决于QDE-1也取决于QDE-3。值得注意的是，我们的结果表明QDE-1是产生aRNA的DNA依赖性RNA聚合酶。此外，Neurospora RNA干扰突变体显示出对DNA损伤的敏感性增加，表明qiRNA通过抑制蛋白质翻译而在DNA损伤反应中发挥作用。

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  • 来源
    《Nature》 |2009年第7244期|274-277|共4页
  • 作者

    Heng-Chi Lee; Shwu-Shin Chang; Swati Choudhary; Antti P. Aalto; Mekhala Maiti; Dennis H. Bamford; Yi Liu;

  • 作者单位

    Department of Physiology, University of Texas Southwestern Medical Center, 5323 Harry Mines Bouievard, Dallas, Texas 75390, USA;

    Department of Physiology, University of Texas Southwestern Medical Center, 5323 Harry Mines Bouievard, Dallas, Texas 75390, USA;

    Department of Physiology, University of Texas Southwestern Medical Center, 5323 Harry Mines Bouievard, Dallas, Texas 75390, USA;

    Institute of Biotechnology and Department of Biological and Environmental Sciences, Biocenter 2, PO Box 56, FIN-00014 University of Helsinki, Helsinki, Finland;

    Department of Physiology, University of Texas Southwestern Medical Center, 5323 Harry Mines Bouievard, Dallas, Texas 75390, USA Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA;

    Institute of Biotechnology and Department of Biological and Environmental Sciences, Biocenter 2, PO Box 56, FIN-00014 University of Helsinki, Helsinki, Finland;

    Department of Physiology, University of Texas Southwestern Medical Center, 5323 Harry Mines Bouievard, Dallas, Texas 75390, 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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