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Originally published in Science Express on 22 March 2007
Science 27 April 2007:
Vol. 316. no. 5824, pp. 575 - 579
DOI: 10.1126/science.1139089
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Research Articles

Control of Stress-Dependent Cardiac Growth and Gene Expression by a MicroRNA

Eva van Rooij,1 Lillian B. Sutherland,1 Xiaoxia Qi,1 James A. Richardson,1,2 Joseph Hill,3 Eric N. Olson1*

The heart responds to diverse forms of stress by hypertrophic growth accompanied by fibrosis and eventual diminution of contractility, which results from down-regulation of {alpha}–myosin heavy chain ({alpha}MHC) and up-regulation of ßMHC, the primary contractile proteins of the heart. We found that a cardiac-specific microRNA (miR-208) encoded by an intron of the {alpha}MHC gene is required for cardiomyocyte hypertrophy, fibrosis, and expression of ßMHC in response to stress and hypothyroidism. Thus, the {alpha}MHC gene, in addition to encoding a major cardiac contractile protein, regulates cardiac growth and gene expression in response to stress and hormonal signaling through miR-208.

1 Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390–9148, USA.
2 Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390–9148, USA.
3 Department of Internal Medicine, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390–9148, USA.

* To whom correspondence should be addressed. E-mail: eric.olson{at}utsouthwestern.edu

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Science. ISSN 0036-8075 (print), 1095-9203 (online)