Exploiting Drosophila genetics to understand microRNA function and regulation

Although a great deal is known about the identity, biogenesis, and targeting capacity of microRNAs (miRNAs) in animal cells, far less is known about their functional requirements at the organismal level. Much remains to be understood about the necessity of miRNAs for overt phenotypes, the identity of critical miRNA targets, and the control of miRNA transcription. In this review, we provide an overview of genetic strategies to study miRNAs in the Drosophila system, including loss- and gain-of-function techniques, genetic interaction strategies, and transgenic reporters of miRNA expression and activity. As we illustrate the usage of these techniques in intact Drosophila, we see certain recurrent themes for miRNA functions, including energy homeostasis, apoptosis suppression, growth control, and regulation of core cell signaling pathways. Overall, we hope that this exposition of Drosophila genetic techniques, well known to the legions of fly geneticists and used to study all genes, can inform the general miRNA community that focuses on other biochemical, molecular, computational, and structural avenues. Clearly, it is the combination of these myriad techniques that has accelerated miRNA research to its extraordinary pace.