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New Data Identifies microRNA-8 as Essential to Female Mosquito Reproduction

NEW YORK (GenomeWeb) – Researchers from the University of California, Riverside this week reported new data linking a microRNA to key reproductive processes in female mosquitoes, a finding that could led to new ways to control the spread of these disease-carrying insects.

Female mosquitoes require a blood meal for reproduction, which provides the underlying mechanism for the spread of vector-borne diseases in humans including malaria, dengue fever, and West Nile virus.

The acquisition of blood triggers a number of events within several tissues of female mosquitoes, including in the fat body, an adipose tissue involved in energy metabolism, immunity, and reproduction, according to a paper published in the Proceedings of the National Academy of Sciences.

"The adult female mosquito fat body undergoes dynamic changes before and after a blood meal to accommodate ovarian development and other physiological necessities," the UC Riverside team wrote in their paper. "The fundamental step in these events is vitellogenesis, in which the intake of blood induces the synthesis and secretion of yolk protein precursors (YPP) in the fat body and subsequent accumulation in the developing oocytes."

In light of recent studies linking miRNA function to reproductive events in mosquitoes, the scientists previously analyzed the expression of the small, non-coding RNAs in mosquitoes and discovered that one — miR-8 — was over-expressed in the female mosquito fat body after a blood meal.

Hypothesizing that miR-8 may play a role in the regulation of female mosquito adult stages, the researchers functionally characterized the miRNA in the female mosquito fat body by inhibiting its expression systemically in vivo using miR-8 antagonists, as well as by silencing it only at certain times and in certain tissues using a miRNA sponge transgenic method in combination with the yeast transcriptional activator gal4 protein/upstream activating sequence system.

They found that miR-8 depletion in the female mosquito fat body after a blood meal resulted in severe defects linked to ovary development and egg deposition, according to the PNAS paper.

Specifically, systemic or fat body-specific silencing of miR-8 resulted in ovaries with drastically smaller primary follicles and prevented eggs from being deposited properly, suggesting impairment in signaling between the fat body and ovary.

Indeed, miR-8 was found to function as a regulator of reproductive events in this tissue by fine-tuning the expression of the mosquito homolog to Drosophila secreted wingless-interacting molecule (Swim), a binding protein for the signaling molecule wingless (Wg). Rescue experiments restored long-range signaling in the female mosquito fat body.

Overall, the work establishes miR-8 as a fundamental player in the female mosquito fat body and uncovers an "intriguing role for the Wg signaling pathway in the female mosquito fat body and reproduction," the UC Riverside group concluded. "Further investigation of the Wg signaling pathway in the adult mosquito fat body is warranted to determine the exact function of fat body Wg and its role in the regulation of the YPP secretory pathway."

Meanwhile, a fuller understanding of how miRNAs function in mosquito reproduction may "pave the way toward the utilization of these small molecules as novel approaches to control," the scientists wrote.