从抑制到激活的转变：微小RNA可上调翻译。

Switching from repression to activation: microRNAs can up-regulate translation.

作者信息

Vasudevan Shobha, Tong Yingchun, Steitz Joan A

机构信息

Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, Boyer Center for Molecular Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.

出版信息

Science. 2007 Dec 21;318(5858):1931-4. doi: 10.1126/science.1149460. Epub 2007 Nov 29.

DOI:10.1126/science.1149460

PMID:18048652

Abstract

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 (TNFalpha) 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.

摘要

富含AU元件（AREs）和微小RNA靶位点是信使核糖核酸（mRNA）3'非翻译区（3'UTRs）中的保守序列，它们在转录后控制基因表达。在细胞周期停滞时，肿瘤坏死因子-α（TNFα）mRNA中的ARE会转变为翻译激活信号，招募与微小核糖核蛋白（微小RNA核糖核蛋白颗粒，即microRNPs）相关的AGO蛋白（即精氨酸蛋白）和脆性X智力低下相关蛋白1（FXR1）。我们发现人类微小RNA miR369-3可引导这些蛋白质与AREs结合以激活翻译。此外，我们证明，两个经过充分研究的微小RNA——Let-7和合成微小RNA miRcxcr4同样会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会抑制翻译。因此，激活是微小RNA核糖核蛋白颗粒在细胞周期停滞时的共同功能。我们提出，微小RNA核糖核蛋白颗粒对翻译的调控在细胞周期中会在抑制和激活之间振荡。