miR-206 and -486 induce myoblast differentiation by downregulating Pax7.
The Pax7 transcription factor is required for muscle satellite cell biogenesis and specification of the myogenic precursor lineage. Pax7 is expressed in proliferating myoblasts but is rapidly downregulated during differentiation. Here we report that miR-206 and -486 are induced during myoblast differentiation and downregulate Pax7 by directly targeting its 3' untranslated region (UTR). Expression of either of these microRNAs in myoblasts accelerates differentiation, whereas inhibition of these microRNAs causes persistence of Pax7 protein and delays differentiation. A microRNA-resistant form of Pax7 is sufficient to inhibit differentiation. Since both these microRNAs are induced by MyoD and since Pax7 promotes the expression of Id2, an inhibitor of MyoD, our results revealed a bistable switch that exists either in a Pax7-driven myoblast state or a MyoD-driven myotube state.
Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Jordan Hall 1232, Charlottesville, VA 22908, USA.
Bijan K
BK
Dey
Jeffrey
J
Gagan
Anindya
A
Dutta
D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D015536:Down-Regulation; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D024510:Muscle Development / Q000235:genetics / Q000502:physiology; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D032448:Myoblasts, Skeletal / Q000166:cytology* / Q000378:metabolism*; D051763:PAX7 Transcription Factor / Q000235:genetics* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015854:Up-Regulation
D020413:3' Untranslated Regions; D035683:MicroRNAs; C540669:Mirn206 microRNA, mouse; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse