microRNA-1 and microRNA-206 regulate skeletal muscle satellite cell proliferation and differentiation by repressing Pax7.
Skeletal muscle satellite cells are adult stem cells responsible for postnatal skeletal muscle growth and regeneration. Paired-box transcription factor Pax7 plays a central role in satellite cell survival, self-renewal, and proliferation. However, how Pax7 is regulated during the transition from proliferating satellite cells to differentiating myogenic progenitor cells is largely unknown. In this study, we find that miR-1 and miR-206 are sharply up-regulated during satellite cell differentiation and down-regulated after muscle injury. We show that miR-1 and miR-206 facilitate satellite cell differentiation by restricting their proliferative potential. We identify Pax7 as one of the direct regulatory targets of miR-1 and miR-206. Inhibition of miR-1 and miR-206 substantially enhances satellite cell proliferation and increases Pax7 protein level in vivo. Conversely, sustained Pax7 expression as a result of the loss of miR-1 and miR-206 repression elements at its 3' untranslated region significantly inhibits myoblast differentiation. Therefore, our experiments suggest that microRNAs participate in a regulatory circuit that allows rapid gene program transitions from proliferation to differentiation.
Chen
Jian-Fu
JF
McAllister Heart Institute, Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Tao
Yazhong
Y
Li
Juan
J
Deng
Zhongliang
Z
Yan
Zhen
Z
Xiao
Xiao
X
Wang
Da-Zhi
DZ
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D024510:Muscle Development / Q000235:genetics / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology* / Q000254:growth & development* / Q000502:physiology; D032446:Myoblasts / Q000378:metabolism; D051763:PAX7 Transcription Factor / Q000378:metabolism* / Q000502:physiology; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000235:genetics / Q000502:physiology; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D015854:Up-Regulation
D035683:MicroRNAs; C540669:Mirn206 microRNA, mouse; D051763:PAX7 Transcription Factor; D051761:Paired Box Transcription Factors; C497322:Pax7 protein, mouse; D011506:Proteins
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