期刊
CELL METABOLISM
卷 27, 期 5, 页码 1026-+出版社
CELL PRESS
DOI: 10.1016/j.cmet.2018.02.022
关键词
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资金
- DFG (Excellence Cluster Cardio-Pulmonary System [ECCPS] [SFB TRR81 TP A02, SFB 1213, TP A02, B02]
- LOEWE Center for Cell and Gene Therapy
- LOEWE network Medical RNomics''
- German Center for Cardiovascular Research (DZHK)
- Foundation Leducq
Muscle stem cells undergo a dramatic metabolic switch to oxidative phosphorylation during differentiation, which is achieved by massively increased mitochondrial activity. Since expression of the muscle-specific miR-1/133a gene cluster correlates with increased mitochondrial activity during muscle stem cell (MuSC) differentiation, we examined the potential role of miR-1/133a in metabolic maturation of skeletal muscles in mice. We found that miR-1/133a downregulate Mef2A in differentiated myocytes, thereby suppressing the Dlk1-Dio3 gene cluster, which encodes multiple microRNAs inhibiting expression of mitochondrial genes. Loss of miR-1/133a in skeletal muscles or increased Mef2A expression causes continuous high-level expression of the Dlk1-Dio3 gene cluster, compromising mitochondrial function. Failure to terminate the stem cell-like metabolic program characterized by high-level Dlk1-Dio3 gene cluster expression initiates profound changes in muscle physiology, essentially abrogating endurance running. Our results suggest a major role of miR-1/133a in metabolic maturation of skeletal muscles but exclude major functions in muscle development and MuSC maintenance.
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