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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Stabilization of hepatitis C virus RNA by an Ago2-miR-122 complex
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Stabilization of hepatitis C virus RNA by an Ago2-miR-122 complex

机译：通过Ago2-miR-122复合物稳定丙型肝炎病毒RNA

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摘要

MicroRNAs (miRNAs) are small noncoding RNAs that regulate eukaryotic gene expression by binding to regions of imperfect complementarity in mRNAs, typically in the 3' UTR, recruiting an Argonaute (Ago) protein complex that usually results in transla-tional repression or destabilization of the target RNA. The translation and decay of mRNAs are closely linked, competing processes, and whether the miRNA-induced silencing complex (RISC) acts primarily to reduce translation or stability of the mRNA remains controversial. miR-122 is an abundant liver-specific miRNA that is an unusual host factor for hepatitis C virus (HCV), an important cause of liver disease in humans. Prior studies show that it binds the 5' UTR of the messenger-sense HCV RNA genome, stimulating translation and promoting genome replication by an unknown mechanism. Here we show that miR-122 binds HCV RNA in association with Ago2 and that this slows decay of the viral genome in infected cells. The stabilizing action of miR-122 does not require the viral RNA to be translationally active nor engaged in replication, and can be functionally substituted by a nonmethylated 5' cap. Our data demonstrate that a RISC-like complex mediates the stability of HCV RNA and suggest that Ago2 and miR-122 act co-ordinately to protect the viral genome from 5' exonuclease activity of the host mRNA decay machinery. miR-122 thus acts in an unconventional fashion to stabilize HCV RNA and slow its decay, expanding the repertoire of mechanisms by which miRNAs modulate gene expression.
机译：MicroRNA（miRNA）是小的非编码RNA，通过结合mRNA的不完全互补区域（通常在3'UTR中）来调节真核基因表达，募集通常导致翻译抑制或不稳定的Argonaute（Ago）蛋白复合物。靶RNA。 mRNA的翻译和衰减紧密相关，相互竞争，而miRNA诱导的沉默复合物（RISC）是否主要起降低mRNA的翻译或稳定性的作用仍存在争议。 miR-122是一种丰富的肝脏特异性miRNA，是丙型肝炎病毒（HCV）的不常见宿主因子，丙型肝炎病毒是人类肝脏疾病的重要原因。先前的研究表明，它结合了信使HCV RNA基因组的5'UTR，通过未知机制刺激翻译并促进基因组复制。在这里，我们显示miR-122与Ago2结合结合HCV RNA，这减慢了感染细胞中病毒基因组的衰减。 miR-122的稳定作用不需要病毒RNA具有翻译活性或不参与复制，并且可以被非甲基化的5'帽取代。我们的数据表明，类似RISC的复合物可介导HCV RNA的稳定性，并表明Ago2和miR-122协同作用来保护病毒基因组免受宿主mRNA衰变机制的5'核酸外切酶活性的影响。因此，miR-122以非常规的方式发挥作用，以稳定HCV RNA并减缓其衰减，从而扩展了miRNA调节基因表达的机制。

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    Tetsuro Shimakami; Daisuke Yamane; Rohit K. Jangra; Brian J. Kempf; Carolyn Spaniel; David J. Barton; Stanley M. Lemon;

  • 作者单位

    Lineberger Comprehensive Cancer Center and Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7292;

    Lineberger Comprehensive Cancer Center and Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7292;

    Lineberger Comprehensive Cancer Center and Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7292;

    Department of Microbiology, University of Colorado School of Medicine, Aurora, CO 80045;

    Lineberger Comprehensive Cancer Center and Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7292;

    Department of Microbiology, University of Colorado School of Medicine, Aurora, CO 80045;

    Lineberger Comprehensive Cancer Center and Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7292;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    RNA decay; viral host factor;

    机译：RNA衰变;病毒宿主因子;

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