Alternative Polyadenylation Mediates MicroRNA Regulation of Muscle Stem Cell Function

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.