Widespread changes in protein synthesis induced by microRNAs
Widespread changes in protein synthesis induced by microRNAs
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DOI：
10.1038/nature07228
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发表时间：
2008-09-04
期刊：
影响因子：
64.8
通讯作者：
Rajewsky, Nikolaus
中科院分区：
文献类型：
--
作者：
Selbach, Matthias;Schwanhaeusser, Bjoern;Rajewsky, Nikolaus
动物微小RNA（miRNAs）通过抑制靶信使RNA的翻译和/或诱导靶信使RNA的降解来调节基因表达。目前还不清楚在全基因组范围内miRNA对翻译的控制程度。我们使用一种新的蛋白质组学方法来测量响应于miRNA转染或内源性miRNA敲低的数千种蛋白质合成的变化。同时，我们使用微阵列定量mRNA水平。在这里，我们发现一个miRNA可以抑制数百种蛋白质的产生，但这种抑制通常相对温和。一些已知的特征的小RNA结合位点，如种子序列，也支配着人类蛋白质合成的抑制，我们报告了额外的靶序列特征。我们证明，除了下调mRNA水平外，miRNA还直接抑制数百个基因的翻译。最后，我们的数据表明，一个miRNA可以通过直接或间接的影响，调节数千个基因的蛋白质合成。
Animal microRNAs ( miRNAs) regulate gene expression by inhibiting translation and/ or by inducing degradation of target messenger RNAs. It is unknown how much translational control is exerted by miRNAs on a genome- wide scale. We used a new proteomic approach to measure changes in synthesis of several thousand proteins in response to miRNA transfection or endogenous miRNA knockdown. In parallel, we quantified mRNA levels using microarrays. Here we show that a single miRNA can repress the production of hundreds of proteins, but that this repression is typically relatively mild. A number of known features of the miRNA- binding site such as the seed sequence also govern repression of human protein synthesis, and we report additional target sequence characteristics. We demonstrate that, in addition to downregulating mRNA levels, miRNAs also directly repress translation of hundreds of genes. Finally, our data suggest that a miRNA can, by direct or indirect effects, tune protein synthesis from thousands of genes.