title: Alternative polyadenylation mediates microRNA regulation of muscle stem cell function.
abstract: Pax3, a key myogenic regulator, is transiently expressed during activation of adult muscle stem cells, or satellite cells (SCs), and is also expressed in a subset of quiescent SCs (QSCs), but only in specific muscles. The mechanisms regulating these variations in expression are not well understood. Here we show that Pax3 levels are regulated by miR-206, a miRNA with a previously demonstrated role in myogenic differentiation. In most QSCs and activated SCs, miR-206 expression suppresses Pax3 expression. Paradoxically, QSCs that express high levels of Pax3 also express high levels of miR-206. In these QSCs, Pax3 transcripts are subject to alternative polyadenylation, resulting in transcripts with shorter 3' untranslated regions (3'UTRs) that render them resistant to regulation by miR-206. Similar alternate polyadenylation of the Pax3 transcript also occurs in myogenic progenitors during development. Our findings may reflect a general role of alternative polyadenylation in circumventing miRNA-mediated regulation of stem cell function.
authors.affiliation: The Glenn Laboratories for the Biology of Aging, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Stéphane C
authors.initials: SC
authors.lastname: Boutet
authors.forename: Tom H
authors.initials: TH
authors.lastname: Cheung
authors.forename: Navaline L
authors.initials: NL
authors.lastname: Quach
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Sara L
authors.initials: SL
authors.lastname: Prescott
authors.forename: Abdolhossein
authors.initials: A
authors.lastname: Edalati
authors.forename: Kevin
authors.initials: K
authors.lastname: Iori
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Rando
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004622:Embryo, Mammalian; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D032446:Myoblasts / Q000378:metabolism*; D051761:Paired Box Transcription Factors / Q000235:genetics; D026723:Polyadenylation; D016133:Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D051761:Paired Box Transcription Factors