The role of the heterogeneous nuclear ribonucleoprotein (hnRNP) Hrb27C in regulating lipid storage in the Drosophila fat body.

The storage of excess nutrients as triglycerides is essential for all organisms to survive when food is scarce; however, the mechanisms by which triglycerides are stored are not completely understood. Genome-wide RNAi screens in Drosophila cells have identified genes involved in mRNA splicing that are important in the regulation of triglyceride storage. Our lab has identified a number of splicing factors important for regulating lipid metabolism; however, the full complement of splicing proteins involved in achieving metabolic homeostasis is unknown. Heterogeneous nuclear ribonucleoproteins (hnRNPs), RNA binding proteins that inhibit the splicing of introns by preventing the assembly of splicing complexes, have no established metabolic functions. To assess any metabolic functions of hnRNPs, we used the GAL4/UAS system to induce RNAi to six hnRNP's: hnRNP-K, rumpelstiltskin (rump), smooth (sm), Hrb27C (also referred to as Hrp48), Hrb98DE, and Hrb87F in the Drosophila fat body. Decreasing the levels of hnRNP-K and rump resulted in a decrease in triglyceride storage, whereas decreasing the levels of sm, Hrb27C, and Hrb98DE resulted in an increase in triglyceride storage. The excess triglyceride phenotype in Hrb27C-RNAi flies resulted from both an increase in the number of fat body cells and the amount of fat stored per cell. In addition, both the splicing of the β-oxidation gene, CPT1, and the expression of the lipase brummer (bmm) was altered in flies with decreased Hrb27C, providing insight into the lipid storage phenotype in these flies. Together, these results suggest that the hnRNP family of splicing factors have varying metabolic functions and may act on specific metabolic genes to control their expression and processing.