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Originally published In Press as doi:10.1074/jbc.M709614200 on February 15, 2008

J. Biol. Chem., Vol. 283, Issue 15, 9836-9843, April 11, 2008
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MicroRNA-26a Targets the Histone Methyltransferase Enhancer of Zeste homolog 2 during Myogenesis*

Chung Fai Wong and Ross L. Tellam1

From the CSIRO Livestock Industries, Queensland Bioscience Precinct, 306 Carmody Rd, St. Lucia 4067, QLD, Australia

MicroRNA (miRNA) are important regulators of many bioxlogical 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.


Received for publication, November 26, 2007 , and in revised form, February 14, 2008.

* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 To whom correspondence should be addressed. Tel.: 61-7-3214-2476; Fax: 61-7-3214-2900; E-mail: Ross.Tellam{at}csiro.Au.


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J. Xu and C. Wong
A computational screen for mouse signaling pathways targeted by microRNA clusters
RNA, July 1, 2008; 14(7): 1276 - 1283.
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