4.7 Article

Regulation of the RNA-binding protein Smaug by the GPCR Smoothened via the kinase Fused

期刊

EMBO REPORTS
卷 21, 期 7, 页码 -

出版社

WILEY
DOI: 10.15252/embr.201948425

关键词

Drosophila; Hedgehog; SAMD4; Smaug; Smoothened

资金

  1. NICHD
  2. ARC
  3. region Ile de France (SESAME)
  4. Paris-Diderot University
  5. Paris-Diderot University (ARS)
  6. CNRS
  7. University of Paris
  8. Fondation ARC pour la Recherche sur le Cancer [1112]
  9. ECOSSud
  10. l'Association Franco-argentine
  11. Fondation ARC pour la Recherche sur le Cancer
  12. CONICETArgentina
  13. Paris Sorbonne Cite

向作者/读者索取更多资源

From fly to mammals, the Smaug/Samd4 family of prion-like RNA-binding proteins control gene expression by destabilizing and/or repressing the translation of numerous target transcripts. However, the regulation of its activity remains poorly understood. We show that Smaug's protein levels and mRNA repressive activity are downregulated by Hedgehog signaling in tissue culture cells. These effects rely on the interaction of Smaug with the G-protein coupled receptor Smoothened, which promotes the phosphorylation of Smaug by recruiting the kinase Fused. The activation of Fused and its binding to Smaug are sufficient to suppress its ability to form cytosolic bodies and to antagonize its negative effects on endogenous targets. Importantly, we demonstrate in vivo that HH reduces the levels of smaug mRNA and increases the level of several mRNAs downregulated by Smaug. Finally, we show that Smaug acts as a positive regulator of Hedgehog signaling during wing morphogenesis. These data constitute the first evidence for a post-translational regulation of Smaug and reveal that the fate of several mRNAs bound to Smaug is modulated by a major signaling pathway.

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