MicroRNA-277 targets insulin-like peptides 7 and 8 to control lipid metabolism and reproduction in Aedes aegypti mosquitoes

Significance Hematophagous female mosquitoes transmit devastating human diseases. Owing to their obligatory blood feeding, they require an extremely high level of lipid metabolism for reproduction. We found that microRNA-277 (miR-277) plays a critical role in lipid metabolism of Aedes aegypti mosquitoes. The genetic disruption of miR-277 using the CRISPR-Cas9 system showed impairment of both lipid storage and ovarian development. Insulin/FOXO signaling was up-regulated after miR-277 depletion. Comprehensive screening and functional identification revealed that insulin-like peptides ilp7 and ilp8 are direct targets of miR-277. CRISPR-Cas9 depletions identified differential actions of these ILPs in lipid accumulation and utilization. Thus, miR-277 serves as a monitor that controls ILP7 and ILP8 mRNA levels to maintain the lipid homeostasis required for reproduction.