title: miR-26a is required for skeletal muscle differentiation and regeneration in mice.
abstract: Multiple microRNAs are known to be induced during the differentiation of myoblasts to myotubes. Yet, experiments in animals have not provided clear evidence for the requirement of most of these microRNAs in myogenic differentiation in vivo. miR-26a is induced during skeletal muscle differentiation and is predicted to target a well-known inhibitor of differentiation, the transforming growth factor β/bone morphogenetic protein (TGF-β/BMP) signaling pathway. Here we show that exogenous miR-26a promotes differentiation of myoblasts, while inhibition of miR-26a by antisense oligonucleotides or by Tough-Decoys delays differentiation. miR-26a targets the transcription factors Smad1 and Smad4, critical for the TGF-β/BMP pathway, and expression of microRNA-resistant forms of these transcription factors inhibits differentiation. Injection of antagomirs specific to miR-26a into neonatal mice derepressed both Smad expression and activity and consequently inhibited skeletal muscle differentiation. In addition, miR-26a is induced during skeletal muscle regeneration after injury. Inhibiting miR-26a in the tibialis anterior muscles through the injection of adeno-associated virus expressing a Tough-Decoy targeting miR-26a prevents Smad down-regulation and delays regeneration. These findings provide evidence for the requirement of miR-26a for skeletal muscle differentiation and regeneration in vivo.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
authors.forename: Bijan K
authors.initials: BK
authors.lastname: Dey
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Gagan
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yan
authors.forename: Anindya
authors.initials: A
authors.lastname: Dutta
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D049109:Cell Proliferation; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D020320:Oligoribonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D051763:PAX7 Transcription Factor / Q000378:metabolism; D012038:Regeneration / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; C543693:Mirn26 microRNA, mouse; D020320:Oligoribonucleotides, Antisense; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; D014157:Transcription Factors