期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 114, 期 43, 页码 E8996-E9005出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1708725114
关键词
Staufen1; MyoD; quiescence; satellite cell; muscle stem cell
资金
- Glenn Foundation for Medical Research
- Muscular Dystrophy Association [MDA313960]
- Facioscapulohumeral Muscular Dystrophy Society
- NIH [R01 AR062185, R37 AG023806, P01 AG036695]
- Department of Veterans Affairs (Biomedical Laboratory RD Merit Review)
Tissue regeneration depends on the timely activation of adult stem cells. In skeletal muscle, the adult stem cells maintain a quiescent state and proliferate upon injury. We show that muscle stem cells (MuSCs) use direct translational repression to maintain the quiescent state. High-resolution single-molecule and single-cell analyses demonstrate that quiescent MuSCs express high levels of Myogenic Differentiation 1 (MyoD) transcript in vivo, whereas MyoD protein is absent. RNA pulldowns and costainings show that MyoD mRNA interacts with Staufen1, a potent regulator of mRNA localization, translation, and stability. Staufen1 prevents MyoD translation through its interaction with the MyoD 3'-UTR. MuSCs from Staufen1 heterozygous (Staufen1(+/-)) mice have increased MyoD protein expression, exit quiescence, and begin proliferating. Conversely, blocking MyoD translation maintains the quiescent phenotype. Collectively, our data show that MuSCs express MyoD mRNA and actively repress its translation to remain quiescent yet primed for activation.
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