| First Author | Heidersbach A | Year | 2013 |
| Journal | Elife | Volume | 2 |
| Pages | e01323 | PubMed ID | 24252873 |
| Mgi Jnum | J:207845 | Mgi Id | MGI:5559809 |
| Doi | 10.7554/eLife.01323 | Citation | Heidersbach A, et al. (2013) microRNA-1 regulates sarcomere formation and suppresses smooth muscle gene expression in the mammalian heart. Elife 2:e01323 |
| abstractText | microRNA-1 (miR-1) is an evolutionarily conserved, striated muscle-enriched miRNA. Most mammalian genomes contain two copies of miR-1, and in mice, deletion of a single locus, miR-1-2, causes incompletely penetrant lethality and subtle cardiac defects. Here, we report that deletion of miR-1-1 resulted in a phenotype similar to that of the miR-1-2 mutant. Compound miR-1 knockout mice died uniformly before weaning due to severe cardiac dysfunction. miR-1-null cardiomyocytes had abnormal sarcomere organization and decreased phosphorylation of the regulatory myosin light chain-2 (MLC2), a critical cytoskeletal regulator. The smooth muscle-restricted inhibitor of MLC2 phosphorylation, Telokin, was ectopically expressed in the myocardium, along with other smooth muscle genes. miR-1 repressed Telokin expression through direct targeting and by repressing its transcriptional regulator, Myocardin. Our results reveal that miR-1 is required for postnatal cardiac function and reinforces the striated muscle phenotype by regulating both transcriptional and effector nodes of the smooth muscle gene expression network. DOI: http://dx.doi.org/10.7554/eLife.01323.001. |
