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Switching from Repression to Activation: MicroRNAs Can Up-Regulate Translation
Shobha Vasudevan,Yingchun Tong,Joan A. Steitz*
AU-rich elements (AREs) and microRNA target sites are conservedsequences in messenger RNA (mRNA) 3' untranslated regions (3'UTRs)that control gene expression posttranscriptionally. Upon cellcycle arrest, the ARE in tumor necrosis factor– (TNF)mRNA is transformed into a translation activation signal, recruitingArgonaute (AGO) and fragile X mental retardation–relatedprotein 1 (FXR1), factors associated with micro-ribonucleoproteins(microRNPs). We show that human microRNA miR369-3 directs associationof these proteins with the AREs to activate translation. Furthermore,we document that two well-studied microRNAs—Let-7 andthe synthetic microRNA miRcxcr4—likewise induce translationup-regulation of target mRNAs on cell cycle arrest, yet theyrepress translation in proliferating cells. Thus, activationis a common function of microRNPs on cell cycle arrest. We proposethat translation regulation by microRNPs oscillates betweenrepression and activation during the cell cycle.
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.
* To whom correspondence should be addressed. E-mail: joan.steitz{at}yale.edu
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