Characterization of microRNA-33 in Drosophila melanogaster
Research in metabolic syndrome in humans has shown that lipid metabolism is a complex set of processes influenced by multiple genes and their regulators. In humans, Srebp, the sterol regulatory element-binding protein gene, encodes a transcription factor that binds to sequences of genes that promote the synthesis of sterols. The focus of this research is the 21 nucleotide long microRNA-33 found in the intron of the Srebp homolog in Drosophila melanogaster. MicroRNAs inhibit protein expression post-transcriptionally by binding to the 3’ UTR of mRNA transcripts to induce their degradation or inhibit translation. Previous research in human hepatic cells suggests that overexpression of miR-33 causes a decrease in β-oxidation and increase in lipid accumulation. In contrast to these findings, previous research in this lab shows a decrease in triglyceride levels in the fat bodies of miR-33 overexpressing adult flies, possibly through a decrease in triglyceride synthesis. To further understand the role of miR-33 in regulating lipid levels in flies, we examined the effects on lipid storage caused by the knockout of miR-33. Our preliminary results show an increase in triglyceride levels in miR-33 knockout flies. Because triglycerides and sterols are important in ovary and oocyte development, we looked for defects in ovary morphology. Abnormalities were found in nurse cells, border cells, and follicle cells of mutant fly egg chambers. This phenotype suggests that miR-33 plays a significant role in D. melanogaster oogenesis through lipid regulation. If the role of miR-33 in lipid storage and biosynthesis is conserved in humans, research on miR-33 in D. melanogaster may someday be used to find a mechanism for treating metabolic diseases.
Ronald Yu, Vassar College ’16, Dan Fu Ruan Vassar College ’17 and Prof. Jennifer Kennell