title: MicroRNA-26a targets the histone methyltransferase Enhancer of Zeste homolog 2 during myogenesis.
abstract: MicroRNA (miRNA) are important regulators of many biological processes, but the targets for most miRNA are still poorly defined. In this study, we profiled the expression of miRNA during myogenesis, from proliferating myoblasts through to terminally differentiated myotubes. Microarray results identified six significantly differentially expressed miRNA that were more than 2-fold different in myotubes. From this list, miRNA-26a (miR-26a), an up-regulated miRNA, was further examined. Overexpression of miR-26a in murine myogenic C2C12 cells induced creatine kinase activity, an enzyme that markedly increases during myogenesis. Further, myoD and myogenin mRNA expression levels were also up-regulated. These results suggest that increased expression of miR-26a promotes myogenesis. Through a bioinformatics approach, we identified the histone methyltransferase, Enhancer of Zeste homolog 2 (Ezh2), as a potential target of miR-26a. Overexpression of miR-26a suppressed the activity of a luciferase reporter construct fused with the 3'-untranslated region of Ezh2. In addition, miR-26a overexpression decreased Ezh2 mRNA expression. These results reveal a model of regulation during myogenesis whereby the up-regulation of miR-26a acts to post-transcriptionally repress Ezh2, a known suppressor of skeletal muscle cell differentiation.
authors.affiliation: CSIRO Livestock Industries, Queensland Bioscience Precinct, 306 Carmody Road, St. Lucia 4067, QLD, Australia.
authors.forename: Chung Fai
authors.initials: CF
authors.lastname: Wong
authors.forename: Ross L
authors.initials: RL
authors.lastname: Tellam
mesh_terms: D020413:3' Untranslated Regions / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D003402:Creatine Kinase / Q000378:metabolism; D000071221:Enhancer of Zeste Homolog 2 Protein; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000096:biosynthesis*; D051379:Mice; D035683:MicroRNAs / Q000096:biosynthesis*; D024510:Muscle Development / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000201:enzymology*; D017570:MyoD Protein / Q000096:biosynthesis; D032446:Myoblasts / Q000166:cytology / Q000201:enzymology*; D018008:Myogenin / Q000096:biosynthesis; D020411:Oligonucleotide Array Sequence Analysis; D063151:Polycomb Repressive Complex 2; D011496:Protein Methyltransferases; D011506:Proteins / Q000378:metabolism*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D018008:Myogenin; D011506:Proteins; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D063151:Polycomb Repressive Complex 2; D003402:Creatine Kinase