title: The RNA-binding protein Staufen1 impairs myogenic differentiation via a c-myc-dependent mechanism.
abstract: Recent work has shown that Staufen1 plays key roles in skeletal muscle, yet little is known about its pattern of expression during embryonic and postnatal development. Here we first show that Staufen1 levels are abundant in mouse embryonic muscles and that its expression decreases thereafter, reaching low levels in mature muscles. A similar pattern of expression is seen as cultured myoblasts differentiate into myotubes. Muscle degeneration/regeneration experiments revealed that Staufen1 increases after cardiotoxin injection before returning to the low levels seen in mature muscles. We next prevented the decrease in Staufen1 during differentiation by generating stable C2C12 muscle cell lines overexpressing Staufen1. Cells overexpressing Staufen1 differentiated poorly, as evidenced by reductions in the differentiation and fusion indices and decreases in MyoD, myogenin, MEF2A, and MEF2C, independently of Staufen-mediated mRNA decay. However, levels of c-myc, a factor known to inhibit differentiation, were increased in C2C12 cells overexpressing Staufen1 through enhanced translation. By contrast, the knockdown of Staufen1 decreased c-myc levels in myoblasts. Collectively our results show that Staufen1 is highly expressed during early stages of differentiation/development and that it can impair differentiation by regulating c-myc, thereby highlighting the multifunctional role of Staufen1 in skeletal muscle cells.
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
authors.forename: Aymeric
authors.initials: A
authors.lastname: Ravel-Chapuis
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
authors.forename: Tara E
authors.initials: TE
authors.lastname: Crawford
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Blais-Crépeau
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
authors.forename: Guy
authors.initials: G
authors.lastname: Bélanger
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
authors.forename: Chase T
authors.initials: CT
authors.lastname: Richer
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada jasmin@uottawa.ca.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Jasmin
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D064326:MEF2 Transcription Factors / Q000096:biosynthesis; D051379:Mice; D024510:Muscle Development; D009132:Muscles / Q000378:metabolism; D017570:MyoD Protein / Q000096:biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D012038:Regeneration / Q000235:genetics
chemical_list: D064326:MEF2 Transcription Factors; C578036:Mef2a protein, mouse; C578041:Mef2c protein, mouse; C489428:Myc protein, mouse; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D016271:Proto-Oncogene Proteins c-myc; D016601:RNA-Binding Proteins; C492187:Stau1 protein, mouse