Switching from Repression to Activation: MicroRNAs Can Up-Regulate Translation
Top Cited Papers
- 21 December 2007
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 318 (5858), 1931-1934
- https://doi.org/10.1126/science.1149460
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–α (TNFα) 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.Keywords
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