The impact of microRNAs on protein output.

The impact of microRNAs on protein output.
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DOI:
10.1038/nature07242
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发表时间:
2008-09-04
期刊:
影响因子:
64.8
通讯作者:
Bartel, David P.
Bartel, David P.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Baek, Daehyun;Villen, Judit;Shin, Chanseok;Camargo, Fernando D.;Gygi, Steven P.;Bartel, David P.

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microRNA是内源性的23个核苷酸的RNA,可以与蛋白质编码基因的信使RNA中的位点配对,以下调这些信息的表达。已知MicroRNA影响许多mRNA的进化和稳定性,但它们对蛋白质输出的整体影响尚未得到研究。在这里,我们使用定量质谱法来测量将microRNA引入培养细胞后以及在小鼠中性粒细胞中删除mir-223后数千种蛋白质的反应。应答蛋白的身份表明,靶向主要是通过位于3′非翻译区中有利的预测背景内的种子匹配位点。数以百计的基因被个体microRNA直接抑制,尽管每一个都是适度的。虽然一些目标被抑制而mRNA水平没有可检测的变化,但那些被三分之一以上抑制的目标也显示出可检测的mRNA不稳定,并且对于更高度抑制的目标,mRNA不稳定通常包括抑制的主要成分。microRNA对蛋白质组的影响表明,对于大多数相互作用,microRNA起着变阻器的作用,对蛋白质输出进行微调。
MicroRNAs are endogenous ∼23-nucleotide RNAs that can pair to sites in the messenger RNAs of protein-coding genes to downregulate the expression from these messages. MicroRNAs are known to influence the evolution and stability of many mRNAs, but their global impact on protein output had not been examined. Here we use quantitative mass spectrometry to measure the response of thousands of proteins after introducing microRNAs into cultured cells and after deleting mir-223 in mouse neutrophils. The identities of the responsive proteins indicate that targeting is primarily through seed-matched sites located within favourable predicted contexts in 3′ untranslated regions. Hundreds of genes were directly repressed, albeit each to a modest degree, by individual microRNAs. Although some targets were repressed without detectable changes in mRNA levels, those translationally repressed by more than a third also displayed detectable mRNA destabilization, and, for the more highly repressed targets, mRNA destabilization usually comprised the major component of repression. The impact of microRNAs on the proteome indicated that for most interactions microRNAs act as rheostats to make fine-scale adjustments to protein output.
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