37 Oral - Physiology, Aging, and Metabolism I
Thursday April 07, 5:45 PM - 6:00 PM

Authors:
Arely V. Diaz; Kelsey Hazegh; Tânia Reis

Affiliation: University of Colorado, Anschutz Medical Campus

Keywords:
b. metabolism; u. RNA binding proteins

Metabolism in males and females is fundamentally different. We found dimorphic expression of sex-determining genes in metabolic tissues (the fat body) and investigated the underlying molecular mechanisms. We previously found that Spenito (Nito), an RNA-binding protein and a subunit of the N6-methyladenosine (m⁶A) methyltransferase complex, is required for proper fat storage. Through its m⁶A RNA modification role, Nito is essential for splicing of sex determination genes and consequently for proper sex establishment. We propose a similar role for Nito in the establishment of metabolic sexual dimorphisms. Fat body-specific Nito knockdown recapitulated the lean phenotype and abolishes fat differences between males and females. To address the requirement of m⁶A, we knocked down other members of the complex. Fat body-specific knockdown of three other members of the m⁶A complex also made larvae lean, but the differences between the sexes were mostly preserved. At the molecular level, Nito was also required to maintain sex-specific fat body identity: Nito depletion caused mis-splicing of Sxl, a master regulator of the sex determination cascade, masculinizing the expression profile of female fat bodies. Altogether, our findings support a model in which Nito establishes differential expression of target genes in males versus females, leading to sexual dimorphisms in fat storage.