title: HuR and miR-1192 regulate myogenesis by modulating the translation of HMGB1 mRNA.
abstract: Upon muscle injury, the high mobility group box 1 (HMGB1) protein is upregulated and secreted to initiate reparative responses. Here we show that HMGB1 controls myogenesis both in vitro and in vivo during development and after adult muscle injury. HMGB1 expression in muscle cells is regulated at the translational level: the miRNA miR-1192 inhibits HMGB1 translation and the RNA-binding protein HuR promotes it. HuR binds to a cis-element, HuR binding sites (HuRBS), located in the 3'UTR of the HMGB1 transcript, and at the same time miR-1192 is recruited to an adjacent seed element. The binding of HuR to the HuRBS prevents the recruitment of Argonaute 2 (Ago2), overriding miR-1192-mediated translation inhibition. Depleting HuR reduces myoblast fusion and silencing miR-1192 re-establishes the fusion potential of HuR-depleted cells. We propose that HuR promotes the commitment of myoblasts to myogenesis by enhancing the translation of HMGB1 and suppressing the translation inhibition mediated by miR-1192.
authors.affiliation: 1] McGill University, Biochemistry Department, Goodman Cancer Center, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6 [2].
authors.forename: Virginie
authors.initials: V
authors.lastname: Dormoy-Raclet
authors.forename: Anne
authors.initials: A
authors.lastname: Cammas
authors.forename: Barbara
authors.initials: B
authors.lastname: Celona
authors.forename: Xian Jin
authors.initials: XJ
authors.lastname: Lian
authors.forename: Kate
authors.initials: K
authors.lastname: van der Giessen
authors.forename: Marija
authors.initials: M
authors.lastname: Zivojnovic
authors.forename: Silvia
authors.initials: S
authors.lastname: Brunelli
authors.forename: Francesca
authors.initials: F
authors.lastname: Riuzzi
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Sorci
authors.forename: Brian T
authors.initials: BT
authors.lastname: Wilhelm
authors.forename: Sergio
authors.initials: S
authors.lastname: Di Marco
authors.forename: Rosario
authors.initials: R
authors.lastname: Donato
authors.forename: Marco E
authors.initials: ME
authors.lastname: Bianchi
authors.forename: Imed-Eddine
authors.initials: IE
authors.lastname: Gallouzi
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002457:Cell Extracts; D002460:Cell Line; D051959:ELAV Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D024243:HMGB1 Protein / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D024510:Muscle Development / Q000235:genetics*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D032446:Myoblasts / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D002457:Cell Extracts; D051959:ELAV Proteins; D024243:HMGB1 Protein; C586895:MIRN1192 microRNA, mouse; D035683:MicroRNAs; D012333:RNA, Messenger