Alternative Polyadenylation Mediates MicroRNA Regulation of Muscle Stem Cell Function

• Published in: Cell stem cell Vol. 10; no. 3; pp. 327 - 336
• Main Authors: Boutet, Stéphane C., Cheung, Tom H., Quach, Navaline L., Liu, Ling, Prescott, Sara L., Edalati, Abdolhossein, Iori, Kevin, Rando, Thomas A.
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 02.03.2012; Cell Press
• Subjects: adults; Animals; Biological and medical sciences; Cell differentiation, maturation, development, hematopoiesis; Cell Line; Cell physiology; Cells, Cultured; Cloning, Molecular; Embryo, Mammalian; Fluorescent Antibody Technique; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; HEK293 Cells; Humans; Mice; Mice, Inbred C57BL; microRNA; MicroRNAs - genetics; MicroRNAs - metabolism; Models, Biological; Molecular and cellular biology; muscle development; muscles; Myoblasts - metabolism; Paired Box Transcription Factors - genetics; Polyadenylation; Polymerase Chain Reaction; stem cells; Stem Cells - cytology; Stem Cells - metabolism; Gene silencing; Regulation(control); Cell function; RNA interference; Stem cell; Micro RNA; Polyadenylation; Myocyte
• ISSN: 1934-5909; 1875-9777; 1875-9777
• DOI: 10.1016/j.stem.2012.01.017

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. [Display omitted] ► Pax3 is expressed in muscle stem cells only in specific muscles ► In most muscle stem cells, Pax3 levels are regulated miR-206 ► In Pax3+ve cells, alternative polyadenylation yields Pax3 mRNAs with short 3′UTRs ► Pax3 transcripts with short 3′UTRs escape miR-206 regulation