Alternative Polyadenylation Mediates MicroRNA Regulation of Muscle Stem Cell Function

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Alternative Polyadenylation Mediates MicroRNA Regulation of Muscle Stem Cell Function

Authors
Type
Published Article
Journal
Cell Stem Cell
Publisher
Elsevier
Publication Date
Mar 07, 2012
Volume
10
Issue
3
Pages
327–336
Identifiers
DOI: 10.1016/j.stem.2012.01.017
PMID: 22385659
PMCID: PMC3306803
Source
AIMS
Keywords
License
Green

Abstract

These authors contributed equally to this work *Correspondence: [email protected] DOI 10.1016/j.stem.2012.01.017 SUMMARY Pax3, a key myogenic regulator, is transiently ex-pressed 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 varia-tions 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 acti-vated 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 alter-native polyadenylation, resulting in transcripts with shorter 3 0 untranslated regions (3 0 UTRs) that render them resistant to regulation by miR-206. Similar alter-nate 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.

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