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Mol Cell Biol DOI:10.1128/MCB.01222-08

MicroRNA-1 negatively regulates expression of the hypertrophy-associated calmodulin and Mef2a genes.

Publication TypeJournal Article
Year of Publication2009
AuthorsIkeda, S, He, A, Kong, SWon, Lu, J, Bejar, R, Bodyak, N, Lee, K-H, Ma, Q, Kang, PM, Golub, TR, Pu, WT
JournalMol Cell Biol
Date Published2009 Apr
KeywordsAnimals, Calmodulin, Cardiomegaly, Cells, Cultured, Down-Regulation, GATA4 Transcription Factor, Gene Expression Regulation, Heart Failure, Hypertrophy, In Vitro Techniques, MEF2 Transcription Factors, Mice, MicroRNAs, Myocytes, Cardiac, Myogenic Regulatory Factors

Calcium signaling is a central regulator of cardiomyocyte growth and function. Calmodulin is a critical mediator of calcium signals. Because the amount of calmodulin within cardiomyocytes is limiting, the precise control of calmodulin expression is important for the regulation of calcium signaling. In this study, we show for the first time that calmodulin levels are regulated posttranscriptionally in heart failure. The cardiomyocyte-restricted microRNA miR-1 inhibited the translation of calmodulin-encoding mRNAs via highly conserved target sites within their 3' untranslated regions. In keeping with its effect on calmodulin expression, miR-1 downregulated calcium-calmodulin signaling through calcineurin to NFAT. miR-1 also negatively regulated the expression of Mef2a and Gata4, key transcription factors that mediate calcium-dependent changes in gene expression. Consistent with the downregulation of these hypertrophy-associated genes, miR-1 attenuated cardiomyocyte hypertrophy in cultured neonatal rat cardiomyocytes and in the intact adult heart. Our data indicate that miR-1 regulates cardiomyocyte growth responses by negatively regulating the calcium signaling components calmodulin, Mef2a, and Gata4.


Alternate JournalMol. Cell. Biol.
PubMed ID19188439
PubMed Central IDPMC2663304
Grant ListP50 HL074734 / HL / NHLBI NIH HHS / United States
P01 HL074734 / HL / NHLBI NIH HHS / United States
/ / Howard Hughes Medical Institute / United States