The RNA-binding protein Staufen1 impairs myogenic differentiation via a c-myc-dependent mechanism.
Bottom Line: 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.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.
Affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.Show MeSH
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Mentions: Primary human skeletal muscle cells (SkMCs) and myoblasts (HSMM) isolated from normal donors were also used to assess expression of Staufen1 during myogenic differentiation. The switch from high to low serum culture conditions induces myoblasts to exit the cell cycle and initiates differentiation by promoting the fusion of primary myoblasts into elongated, multinucleated myotubes. We thus measured the level of Staufen1 protein expression by Western blot during human primary cell differentiation and observed a progressive decrease in Staufen1 levels as cells differentiate (Figure 3, A and B). In fact, Staufen1 levels steadily decreased within 1–4 d after the switch to low serum, a time corresponding to the engagement of cells into the differentiation process, as confirmed by the induction of myogenin (Figure 3A).
Affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.