Tethering of human Ago proteins to mRNA mimics the miRNA-mediated repression of protein synthesis
Tethering of human Ago proteins to mRNA mimics the miRNA-mediated repression of protein synthesis
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DOI：
10.1261/rna.7131604
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发表时间：
2004-10-01
期刊：
影响因子：
4.5
通讯作者：
Filipowicz, W
中科院分区：
文献类型：
--
作者：
Pillai, RS;Artus, CG;Filipowicz, W
MicroRNAs(MiRNAs)是真核生物中参与调节发育、分化和其他过程的-21个核苷酸长的RNAs。在后生动物中，几乎所有的miRNAs都通过与靶mRNAs的3‘-非翻译区(3’-UTR)不完全碱基配对，以未知的机制抑制蛋白质合成来控制基因的表达。也不清楚包含错配和凸起的miRNA-mRNA双链是否提供了特定的特征，这些特征可以被介导抑制的因子识别。MiRNAs构成核糖核蛋白复合体的一部分，miRNPs含有ArgAerte(AGO)和其他蛋白质。在这里，我们证明了miRNAs对翻译的影响可以在人类HeLa细胞中通过不依赖于miRNA的AGO蛋白与报告mRNA的3‘-UTR的捆绑来模拟。蛋白质合成的抑制发生在报告mRNA水平没有改变的情况下，并且依赖于将hAgo2拴在3‘-UTR上的发夹的数量，而不是位置。这些发现表明，miRNAs的一个主要功能是引导它们的相关蛋白与mRNA结合。
MicroRNAs (miRNAs) are -21-nt-long RNAs involved in regulating development, differentiation, and other processes in eukaryotes. In metazoa, nearly all miRNAs control gene expression by imperfectly base-pairing with the 3'-untranslated region (3'-UTR) of target mRNAs and repressing protein synthesis by an unknown mechanism. It is also unknown whether miRNA-mRNA duplexes containing mismatches and bulges provide specific features that are recognized by factors mediating the repression. miRNAs form part of ribonucleoprotein complexes, miRNPs, that contain Argonaute (Ago) and other proteins. Here we demonstrate that effects of miRNAs on translation can be mimicked in human HeLa cells by the miRNA-independent tethering of Ago proteins to the 3'-UTR of a reporter mRNA. inhibition of protein synthesis occurred without a change in the reporter mRNA level and was dependent on the number, but not the position, of the hairpins tethering hAgo2 to the 3'-UTR. These findings indicate that a primary function of miRNAs is to guide their associated proteins to the mRNA.