4.8 Article

microRNA-1 regulates sarcomere formation and suppresses smooth muscle gene expression in the mammalian heart

期刊

ELIFE
卷 2, 期 -, 页码 -

出版社

ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.01323

关键词

-

类别

资金

  1. National Science Foundation
  2. National Institutes of Health [U01 HL100406, U01 HL098179, R01 HL057181, P01 HL089707]
  3. American Heart Association
  4. Amyotrophic Lateral Sclerosis Association
  5. California Institute for Regenerative Medicine
  6. William Younger Family Foundation
  7. LK Whittier Foundation
  8. Roddenberry Foundation

向作者/读者索取更多资源

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.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.8
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据