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: To complement these morphological analyses and further characterize the differentiation defects, we analyzed expression of two key muscle genes expressed during the early and later stages of muscle differentiation. Protein and mRNA expression were determined via Western blot and real-time quantitative reverse transcription-PCR (qRT-PCR), respectively. Our results show that overexpression of Staufen1-HA induced a dramatic reduction (p < 0.001) in the expression of myogenin and MyHC in clones #15 and #25 as assessed by Western blotting (Figure 5, A–C). The decrease in myogenin expression was also confirmed (p < 0.05) at the transcript level by qRT-PCR (Figure 5D).
Affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.