Journal Article

Staufen1 inhibits MyoD translation to actively maintain muscle stem cell quiescence

Klein, Julian D. D., Rando, Thomas A., de Morrée, Antoine, Salvi, Jayesh S., Quarta, Marco, Biressi, Stefano, Gan, Qiang, Akimenko, Igor, van Velthoven, Cindy T. J.

2017

Overview

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.

• Publisher: National Academy of Sciences
• Subject: 3' Untranslated regions / Activation / Animals / Biological Sciences / Cell Biology / Cell Differentiation / Gene Expression Regulation - physiology / Localization / Mice / mRNA stability / Muscle Cells - physiology / Muscles / MyoD protein / MyoD Protein - genetics / MyoD Protein - metabolism / PNAS Plus / Protein expression / Regeneration / Ribonucleic acid / RNA / RNA, Messenger - genetics / RNA, Messenger - metabolism / RNA-Binding Proteins - genetics / RNA-Binding Proteins - metabolism / Skeletal muscle / Stem cell transplantation / Stem cells / Stem Cells - physiology / Tissue engineering / Transcription / Translation