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Publication : The RNA-binding protein Staufen1 impairs myogenic differentiation via a c-myc-dependent mechanism.

First Author  Ravel-Chapuis A Year  2014
Journal  Mol Biol Cell Volume  25
Issue  23 Pages  3765-78
PubMed ID  25208565 Mgi Jnum  J:314894
Mgi Id  MGI:6822734 Doi  10.1091/mbc.E14-04-0895
Citation  Ravel-Chapuis A, et al. (2014) The RNA-binding protein Staufen1 impairs myogenic differentiation via a c-myc-dependent mechanism. Mol Biol Cell 25(23):3765-78
abstractText  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.
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