期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：5
页码：1440-1445
DOI：10.1073/pnas.1424408112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceMosquitoes transmit some of the most devastating human diseases. Acquisition of blood initiates a cascade of events in various tissues in the female mosquito. Here we describe our study using newly established genetic tools in mosquito biology and a comprehensive microRNA target identification analysis to characterize microRNA-8 (miR-8) functionally in Aedes aegypti female mosquitoes. miR-8 works in the fat body by regulating its target, secreted wingless-interacting molecule. miR-8 acts on the long-range Wingless signaling pathway and plays an essential role in the female mosquito fat body controlling the secretory activity of yolk protein precursors required for oocyte development. Thus, this study identifies the fat body specific action of miR-8 and its target in regulating mosquito reproduction. Female mosquitoes require a blood meal for reproduction, and this blood meal provides the underlying mechanism for the spread of many important vector-borne diseases in humans. A deeper understanding of the molecular mechanisms linked to mosquito blood meal processes and reproductive events is of particular importance for devising innovative vector control strategies. We found that the conserved microRNA miR-8 is an essential regulator of mosquito reproductive events. Two strategies to inhibit miR-8 function in vivo were used for functional characterization: systemic antagomir depletion and spatiotemporal inhibition using the miRNA sponge transgenic method in combination with the yeast transcriptional activator gal4 protein/upstream activating sequence system. Depletion of miR-8 in the female mosquito results in defects related to egg development and deposition. We used a multialgorithm approach for miRNA target prediction in mosquito 3' UTRs and experimentally verified secreted wingless-interacting molecule (swim) as an authentic target of miR-8. Our findings demonstrate that miR-8 controls the activity of the long-range Wingless (Wg) signaling by regulating Swim expression in the female fat body. We discovered that the miR-8/Wg axis is critical for the proper secretion of lipophorin and vitellogenin by the fat body and subsequent accumulation of these yolk protein precursors by developing oocytes.
