Female mosquitoes transmit numerous devastating human diseases because they require vertebrate blood meal for egg development. MicroRNAs (miRNAs) play critical roles across multiple reproductive processes in female Aedes aegypti mosquitoes. However, how miRNAs are controlled to coordinate their activity with the demands of mosquito reproduction remains largely unknown. We report that the ecdysone receptor (EcR)–mediated 20-hydroxyecdysone (20E) signaling regulates miRNA expression in female mosquitoes. EcR RNA-interference silencing linked to small RNA-sequencing analysis reveals that EcR not only activates but also represses miRNA expression in the female mosquito fat body, a functional analog of the vertebrate liver. EcR directly represses the expression of clustered miR-275 and miR-305 before blood feeding when the 20E titer is low, whereas it activates their expression in response to the increased 20E titer after a blood meal. Furthermore, we find that SMRTER, an insect analog of the vertebrate nuclear receptor corepressors SMRT and N-CoR, interacts with EcR in a 20E-sensitive manner and is required for EcR-mediated repression of miRNA expression in Ae. aegypti mosquitoes. In addition, we demonstrate that miR-275 and miR-305 directly target glutamate semialdehyde dehydrogenase and AAEL009899, respectively, to facilitate egg development. This study reveals a mechanism for how miRNAs are controlled by the 20E signaling pathway to coordinate their activity with the demands of mosquito reproduction.

雌性蚊子传播许多毁灭性的人类疾病，因为它们需要脊椎动物的血粉来发育卵。 MicroRNA (miRNA) 在雌性埃及伊蚊的多个生殖过程中发挥着关键作用。然而，如何控制 miRNA 来协调其活性与蚊子繁殖的需求仍然很大程度上未知。我们报道，蜕皮激素受体 (EcR) 介导的 20-羟基蜕皮激素 (20E) 信号调节雌性蚊子中的 miRNA 表达。与小 RNA 测序分析相关的 EcR RNA 干扰沉默表明，EcR 不仅激活而且抑制雌性蚊子脂肪体（脊椎动物肝脏的功能类似物）中的 miRNA 表达。当20E滴度较低时，EcR在喂血前直接抑制簇状miR-275和miR-305的表达，而在吸血后20E滴度增加时，EcR激活它们的表达。此外，我们发现SMRTER（脊椎动物核受体辅阻遏物SMRT和N-CoR的昆虫类似物）以20E敏感的方式与EcR相互作用，并且是EcR介导的Ae中miRNA表达抑制所必需的。埃及蚊子。此外，我们证明miR-275和miR-305分别直接靶向谷氨酸半醛脱氢酶和AAEL009899 ，以促进卵子发育。这项研究揭示了 20E 信号通路控制 miRNA 的机制，以协调其活性与蚊子繁殖的需求。