microRNA-1 regulates sarcomere formation and suppresses smooth muscle gene expression in the mammalian heart
| Title: | microRNA-1 regulates sarcomere formation and suppresses smooth muscle gene expression in the mammalian heart |
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| Authors: | Amy Heidersbach, Chris Saxby, Karen Carver-Moore, Yu Huang, Yen-Sin Ang, Pieter J de Jong, Kathryn N Ivey, Deepak Srivastava |
| Source: | eLife, Vol 2 (2013) |
| Publisher Information: | eLife Sciences Publications Ltd, 2013. |
| Publication Year: | 2013 |
| Collection: | LCC:Medicine LCC:Science LCC:Biology (General) |
| Subject Terms: | microRNA-1, cardiac, sarcomere, Telokin, Myocardin, smooth muscle gene expression, Medicine, Science, Biology (General), QH301-705.5 |
| More Details: | 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. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2050-084X |
| Relation: | https://elifesciences.org/articles/01323; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.01323 |
| Access URL: | https://doaj.org/article/7e574b2d00aa47e2b8ec607b379d5148 |
| Accession Number: | edsdoj.7e574b2d00aa47e2b8ec607b379d5148 |
| Database: | Directory of Open Access Journals |
| ISSN: | 2050084X |
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| DOI: | 10.7554/eLife.01323 |
| Published in: | eLife |
| Language: | English |