A-to-I Pre-mRNA Editing in Drosophila Is Primarily Involved in Adult Nervous System Function and Integrity

AbstractSpecific A-to-I RNA editing, like that seen in mammals, has been reported for several Drosophila ion channel genes. Drosophila possesses a candidate editing enzyme, dADAR. Here, we describe dADAR deletion mutants that lack ADAR activity in extracts. Correspondingly, all known Drosophila site-specific RNA editing (25 sites in three ion channel transcripts) is abolished. Adults lacking dADAR are morphologically wild-type but exhibit extreme behavioral deficits including temperature-sensitive paralysis, locomotor uncoordination, and tremors which increase in severity with age. Neurodegeneration accompanies the increase in phenotypic severity. Surprisingly, dADAR mutants are not short-lived. Thus, A-to-I editing of pre-mRNAs in Drosophila acts predominantly through nervous system targets to affect adult nervous system function, integrity, and behavior