Box H/ACA snoRNP regulates lipid storage through insulin signaling pathway in Drosophila melanogaster

Lipid homeostasis is essential for organismal physiology, and its disruption contributes to metabolic disorders. Using an unbiased genetic modifier screen in Drosophila , we identified GAR1, a core component of the box H/ACA small nucleolar ribonucleoprotein complex, as a pivotal regulator of systemic lipid storage. We show that the H/ACA snoRNP complex is essential for maintaining lipid droplet morphology in adipose tissue and preventing ectopic fat accumulation. Moreover, null mutants of Gar1 or Dkc1 exhibit severe developmental defects, including reduced body size and larval lethality. RNA-seq analysis revealed that Gar1 dysfunction triggered widespread alternative splicing defects, specifically targeting key transcripts within the insulin signaling cascade, including chico , Pi3K92E , sgg , and Lip4 . Furthermore, knockdown of Gar1 impaired insulin signaling, as evidenced by the reduced membrane localization of the tGPH fluorescence. Genetic epistasis further positions GAR1 upstream of the lin-28 / foxo axis, as knocking down lin-28 or foxo fully rescues the lipometabolic defects in GAR1-deficient animals. These findings reveal a previously unrecognized link between the snoRNP machinery and metabolic process, establishing the box H/ACA complex as an important coordinator that integrates RNA processing with insulin-mediated nutrient sensing to ensure developmental and lipid homeostasis.