Tissue specific RNAseq of Drosophila mitonuclear strains treated with rapamycin

This study seeks to determine the roles of sex, tissue, mtDNA genotype and rapamycin on the transcriptional profiles of adult Drosophila. RNAseq analyses were conducted on head, thorax and abdomen tissues from female and male Drosophila that had been exposed to normal food vs. food with the mTOR inhibitor rapamycin. The genotypes were D. melanogaster strain OregonR carrying it native OregonR mtDNA, and OregonR carrying the sm21 mtDNA from D. simulans. These strains have been used in previous studies to model a disruption or native mitochondrial-nuclear communication. The motivation for the study was to quantify the effects of these factors on rapamycin-induced gene expression. The pathways downstream of mTOR control a complex network of effects across many cell and tissue types, and the mTOR inhibitor rapamycin is widely used for both clinical and experimental analyses of these pathways. The efficacy of rapamycin as a therapeutic agent is limited by numerous off-target or side effects, due largely to the broad impact of mTOR on cellular function. Many studies have demonstrated that the effect of rapamycin treatment differs between sexes, or tissues, or genotypes. We sought to extend this approach by analyzing the individual and joint effects of these factors to understand the interactions that modify the effects of mTOR and its inhibition by rapamycin. Our study uncovers a wide range of novel interaction effects of rapamycin on gene expression across sexes, tissues and mtDNA genotype. These results are experimentally relevant by contributing knowledge about the specificity of rapamycin as an mTOR inhibitor that may help minimize off target or side effects of treatments.