Notably, these RBPs and their bound mRNAs often form dynamic membrane‐less organelles (ribonucleoprotein (RNP) granules) with liquid droplet‐like behavior and whose assembly can be dynamically regulated in response to external and internal factors 3, 4, 5, 6, 7.

Cytoplasmic mRNA regulation is mediated by RNA‐binding proteins (RBPs) and non‐coding RNAs which co‐recruit specific sets of mRNAs and protein factors that regulate mRNA fate 1. While post‐transcriptional regulation of numerous cytoplasmic transcripts is known to play key roles in gene expression by modulating their stability, localization, and/or translation (see for review 1), knowledge of how these processes are regulated by cell signaling remains rudimentary (see for instance, 2). 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.Ī challenge in cell and developmental biology is to understand how inter‐ and intracellular signaling systems control gene expression. Finally, we show that Smaug acts as a positive regulator of Hedgehog signaling during wing morphogenesis. Importantly, we demonstrate in vivo that HH reduces the levels of smaug mRNA and increases the level of several mRNAs downregulated by Smaug. 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. 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. We show that Smaug's protein levels and mRNA repressive activity are downregulated by Hedgehog signaling in tissue culture cells.

However, the regulation of its activity remains poorly understood. 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.

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