Switching from repression to activation: MicroRNAs can up-regulate translation

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.