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: As a control, we first examined expression of CUGBP1, a developmentally regulated RNA-binding protein in skeletal muscle (Ladd et al., 2001, 2005; Lin et al., 2006). We show that its expression is significantly decreased during skeletal muscle development (p < 0.001), recapitulating expression profiles previously observed (Figure 1, A and B). Then we analyzed Staufen1 levels and showed that Staufen1 is highly abundant in embryonic muscle limbs at E14.5 (Figure 1, A and C). However, expression of Staufen1 decreases gradually (p < 0.001) throughout skeletal muscle mass development, resulting in a low level of expression in mature adult muscle. Because the whole muscle mass was used in these experiments, we cannot exclude that Staufen1 is decreased in several cell types contained within developing muscle tissues. By contrast, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and β-actin were used as loading controls and show increased expression during muscle mass development (Figure 1A). Together these results suggest that expression of the RNA-binding protein Staufen1 is developmentally regulated during mouse skeletal muscle development.
Affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.