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Mammalian microRNAs predominantly act to decrease target mRNA levels

机译:哺乳动物microRNA主要起到降低目标mRNA水平的作用

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摘要

MicroRNAs (miRNAs) are endogenous ~ 22-nucleotide RNAs that mediate important gene-regulatory events by pairing to the mRNAs of protein-coding genes to direct their repression. Repression of these regulatory targets leads to decreased translational efficiency and/or decreased mRNA levels, but the relative contributions of these two outcomes have been largely unknown, particularly for endogenous targets expressed at low-to-moderate levels. Here, we use ribosome profiling to measure the overall effects on protein production and compare these to simultaneously measured effects on mRNA levels. For both ectopic and endogenous miRNA regulatory interactions, lowered mRNA levels account for most (≥84%) of the decreased protein production. These results show that changes in mRNA levels closely reflect the impact of miRNAs on gene expression and indicate that destabilization of target mRNAs is the predominant reason for reduced protein output.
机译:MicroRNA(miRNA)是内源性的22个核苷酸的RNA,通过与蛋白质编码基因的mRNA配对来介导重要的基因调控事件,从而介导重要的基因调控事件。抑制这些调控靶标会导致翻译效率降低和/或mRNA水平下降,但是,这两个结果的相对贡献在很大程度上尚不清楚,尤其是对于以中低水平表达的内源性靶标而言。在这里,我们使用核糖体分析来测量对蛋白质生产的总体影响,并将其与同时测量的对mRNA水平的影响进行比较。对于异位和内源性miRNA调节相互作用,降低的mRNA水平占减少的蛋白质产量的大部分(≥84%)。这些结果表明,mRNA水平的变化紧密反映了miRNA对基因表达的影响,并表明靶标mRNA的不稳定是蛋白质输出减少的主要原因。

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  • 来源
    《Nature》 |2010年第7308期|P.835-840ⅲ|共7页
  • 作者单位

    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA Howard Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;

    rnHoward Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94158, USA California Institute for Quantitative Biosciences, San Francisco, California 94158, USA;

    rnHoward Hughes Medical Institute and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94158, USA California Institute for Quantitative Biosciences, San Francisco, California 94158, USA;

    rnWhitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA Howard Hughes Medical Institute and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, 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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  • 正文语种 eng
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