A-to-I pre-mRNA editing in Drosophila is primarily involved in adult nervous system function and integrity

Specific A-to-I RNA editing, like that seen in mammals, has been reported f or several Drosophila ion channel genes. Drosophila possesses a candidate e diting enzyme, dADAR. Here, we describe dADAR deletion mutants that lack AD AR activity in extracts. Correspondingly, all known Drosophila site-specifi c RNA editing (25 sites in three ion channel transcripts) is abolished. Adu lts lacking dADAR are morphologically wild-type but exhibit extreme behavio ral deficits including temperature-sensitive paralysis, locomotor uncoordin ation, and tremors which increase in severity with age. Neurodegeneration a ccompanies 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.