Adenosine-to-Inosine Genetic Recoding Is Required in the Adult Stage Nervous System for Coordinated Behavior in Drosophila

Adenosine deaminases acting on RNA (ADARs) catalyze the deamination of adenosine to inosine in double-stranded RNA templates, a process known as RNA editing. In Drosophila, multiple ADAR isoforms are generated from a single locus (dAdar) via post-transcriptional modifications. Collectively, these isoforms act to edit a wide range of transcripts involved in neuronal signaling, as well as the precursors of endogenous small interfering RNAs. The phenotypic consequences of a loss of dADAR activity have been well characterized and consist of profound behavioral defects manifested at the adult stage, including extreme uncoordination, seizures, and temperature-sensitive paralysis. However, the spatio-temporal requirements of adenosine to inosine editing for correct behavior are unclear. Using transgenic RNA interference, we show that network-wide editing in the nervous system is required for normal adult locomotion. Regulated restoration of editing activity demonstrates that the neuronal requirement of dADAR activity has a significant adult stage component. Furthermore we show that in relation to behavior there are no observable genetic interactions between dAdar and several loci encoding RNA interference components, suggesting that editing of neuronal transcripts is the key mode of ADAR activity for normal behavior in Drosophila.