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Science 316 (5824): 575-579

Copyright © 2007 by the American Association for the Advancement of Science

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*

Abstract: 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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