Unraveling pleiotropic functions of A-to-I RNA editing in Drosophila

In metazoan cells, transcripts that fold into double-strand RNA structures are endowed with the capacity to undergo A-to-I RNA editing, during which adenosines are catalytically deaminated to inosines by a class of enzymes known as ADARs (adenosine deaminases acting on RNA). In Drosophila, a wide range of coding mRNAs associated with signaling in the nervous system undergo A-to-I editing, and loss of editing results in extreme behavioral defects. Furthermore, there are indications that the precursors of endogenous small interfering RNAs also undergo editing. However, the mechanism by which A-to-I editing is related to ethology in Drosophila is unclear, as are the precise cell-types and developmental stages in which editing is most crucial. We have investigated these issues by altering small RNA production in flies lacking ADAR, and modulating editing levels in both time and space through a variety of transgenic techniques. Our results indicate that genetic re-coding in the nervous system is likely to be the primary pathway through which editing affects behavioral outputs, and further suggest that editing is required to 'fine-tune' neuro-transmission in the adult brain.