Department of Molecular Cell Biology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
Biochem Biophys Res Commun. 2012 Jan 6;417(1):427-32. doi: 10.1016/j.bbrc.2011.11.133. Epub 2011 Dec 7.
Post-transcriptional regulation of gene expression by RNA-binding proteins has pivotal roles in many biological processes. We have shown that Stau1, a conserved RNA-binding protein, negatively regulates myogenesis in C2C12 myoblasts. However, its target mRNAs in regulation of myogenesis remain unknown. Here we describe that Stau1 positively regulates expression of Dvl2 gene encoding a central mediator of Wnt pathway in undifferentiated C2C12 myoblasts. Stau1 binds to 3' untranslated region (UTR) of Dvl2 mRNA and Stau1 knockdown shortened a half-life of the mRNA containing Dvl2 3' UTR. After induction of myogenic differentiation, association of Stau1 with 3' UTR of Dvl2 mRNA was decreased. Correlated with the decrease in the association, the Dvl2 mRNA level was reduced during myogenesis. A forced expression of Dvl2 markedly inhibited progression of myogenic differentiation. Our results suggest that Dvl2 has an inhibitory role in myogenesis and Stau1 coordinates myogenesis through the regulation of Dvl2 mRNA.
RNA 结合蛋白对基因表达的转录后调控在许多生物学过程中起着关键作用。我们已经表明，Stau1 是一种保守的 RNA 结合蛋白，可负调控 C2C12 成肌细胞中的肌发生。然而，其在调节肌发生中的靶 mRNA 仍不清楚。在这里，我们描述了 Stau1 正向调控编码 Wnt 通路中心介质的 Dvl2 基因在未分化的 C2C12 成肌细胞中的表达。Stau1 结合到 Dvl2 mRNA 的 3'非翻译区 (UTR)，Stau1 敲低缩短了含有 Dvl2 3'UTR 的 mRNA 的半衰期。在肌生成分化诱导后，Stau1 与 Dvl2 mRNA 的 3'UTR 的结合减少。与结合减少相关，Dvl2 mRNA 水平在肌生成过程中降低。Dvl2 的强制表达显著抑制肌生成分化的进展。我们的结果表明，Dvl2 在肌发生中具有抑制作用，Stau1 通过调节 Dvl2 mRNA 来协调肌发生。
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