Studying the functional link between RNA editing and complex behavior in Fruit Flies

Adenosine-to-inosine (A-to-I) RNA editing is a co-transcriptional mechanism that serves to diversify the transcriptome by the selective conversion of certain adenosines in RNA substrates to inosines. The recoded inosines are then read by the cellular machinery as guanosine, leading to a variety of consequences such as altering amino acid sequences of proteins. The process is mediated by adenosine deaminase acting on RNA (ADAR) enzymes, and is a neurologically important, and it is thought to "fine-tune" neuro-physiological properties of neurons by diversifying the sequence of ion channels and pre-synaptic proteins participate in neurotransmission. In Drosophila, the knockout of ADAR leads to severe neurological defects such as locomotion impairment, heat sensitive-paralysis, and age-dependent tremors. A-to-I RNA editing is a very widespread phenomenon, with millions of sites in humans, tens of thousands in mice, and thousands in Drosophila, however, only a handful of sites have been functionally studied and it is unknown what fraction of editing events is functionally important. Here, we use Drosophila Melanogaster to dissect the behavioral significance of evolutionary conserved editing site. [o1] We focused our efforts on GluClα, a glutamate-gated chloride ion channel with conserved editing site in its ligand binding domain and studied the link between editing status of this single site and several olfaction related behaviors. Flies harboring an unedited form of the channel display defects in the ability to discriminate appetitive and aversive odors, female flies show delayed receptivity to male courtship attempts, and males exhibit less aggressive behavior.