Switching from repression to activation: MicroRNAs can up-regulate translation
Switching from repression to activation: MicroRNAs can up-regulate translation
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DOI：
10.1126/science.1149460
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发表时间：
2007-12-21
期刊：
影响因子：
56.9
通讯作者：
Steitz, Joan A.
中科院分区：
文献类型：
--
作者：
Vasudevan, Shobha;Tong, Yingchun;Steitz, Joan A.
富含AU的元件（AREs）和微小RNA（microRNA）靶位点是信使RNA（mRNA）3'非翻译区（3' UTRs）中的保守序列，它们在转录后水平调控基因表达。在细胞周期停滞时，肿瘤坏死因子 -α（TNFα）mRNA中的ARE转变为翻译激活信号，招募AGO蛋白（Argonaute）和脆性X智力低下相关蛋白1（FXR1），这些是与微小核糖核蛋白（microRNPs）相关的因子。我们发现人微小RNA miR369 - 3引导这些蛋白与AREs结合以激活翻译。此外，我们证明两种经过充分研究的微小RNA——Let - 7和合成的微小RNA miRcxcr4同样在细胞周期停滞时诱导靶mRNA的翻译上调，但它们在增殖细胞中抑制翻译。因此，激活是微小核糖核蛋白在细胞周期停滞时的一个常见功能。我们提出微小核糖核蛋白对翻译的调控在细胞周期中在抑制和激活之间波动。
AU- rich elements ( AREs) and microRNA target sites are conserved sequences in messenger RNA ( mRNA) 3' untranslated regions ( 3' UTRs) that control gene expression posttranscriptionally. Upon cell cycle arrest, the ARE in tumor necrosis factor-alpha ( TNF alpha) mRNA is transformed into a translation activation signal, recruiting Argonaute ( AGO) and fragile X mental retardation- related protein 1 ( FXR1), factors associated with micro- ribonucleoproteins ( microRNPs). We show that human microRNA miR369-3 directs association of these proteins with the AREs to activate translation. Furthermore, we document that two well- studied microRNAs- Let- 7 and the synthetic microRNA miRcxcr4- likewise induce translation up-regulation of target mRNAs on cell cycle arrest, yet they repress translation in proliferating cells. Thus, activation is a common function of microRNPs on cell cycle arrest. We propose that translation regulation by microRNPs oscillates between repression and activation during the cell cycle.