title: HuR-dependent loading of miRNA RISC to the mRNA encoding the Ras-related small GTPase RhoB controls its translation during UV-induced apoptosis.
abstract: Of critical importance in the stress response is the post-transcriptional control of the expression of important genes involved in the control of cell survival and apoptosis. Here we report that miR-19, an oncogenic component of the miR-17-92/Oncomir-1 microRNA polycistron, regulates the expression of Ras homolog B (RhoB) in keratinocytes upon exposure to ultraviolet (UV) radiation. Strikingly, we could not find any evidence for deregulated expression of miR-19 during UV treatment. However, we show that miR-19-mediated regulation of antiapoptotic RhoB expression requires the binding of human antigen R (HuR), an AU-rich element binding protein, to the 3'-untranslated region of the rhoB mRNA. We propose that the loss of the interdependent binding between HuR and miR-19 to the rhoB mRNA upon UV exposure relieves this mRNA from miR-19-dependent inhibition of translation and contributes to the apoptotic response.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U, Toulouse, France.
authors.forename: V
authors.initials: V
authors.lastname: Glorian
authors.forename: G
authors.initials: G
authors.lastname: Maillot
authors.forename: S
authors.initials: S
authors.lastname: Polès
authors.forename: J S
authors.initials: JS
authors.lastname: Iacovoni
authors.forename: G
authors.initials: G
authors.lastname: Favre
authors.forename: S
authors.initials: S
authors.lastname: Vagner
mesh_terms: D020413:3' Untranslated Regions; D017209:Apoptosis / Q000528:radiation effects*; D001665:Binding Sites; D002460:Cell Line; D051959:ELAV Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D049409:Luciferases, Firefly / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D014466:Ultraviolet Rays; D020743:rhoB GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D051959:ELAV Proteins; C549214:MIRN19A microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D049409:Luciferases, Firefly; D020743:rhoB GTP-Binding Protein