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

Department of Genetics and Developmental Biology, University of Connecticut, Сторс, Connecticut, United States
Cell (Impact Factor: 32.24). 09/2000; 102(4):437-49. DOI: 10.1016/S0092-8674(00)00049-0
Source: PubMed


Specific 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.

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    • "tem undergo A - to - I editing , and loss of editing results in extreme behavioral defects ( Jepson and Reenan , 2009 ; Jepson et al . , 2011 ; Jin et al . , 2007 ; Jones et al . , 2009 ; Maldonado et al . , 2013 ; Palladino et al . , 2000 ) . Eleven A - to - I editing sites have been identified in the DmNa v transcript ( Hanrahan et al . , 2000 ; Palladino et al . , 2000 ; Reenan et al . , 2000 ; Rieder et al . , 2013 ) . The actual number of RNA editing sites may be much greater , because the transcript region examined in these studies represents only a portion of the complete DmNa v open reading frame . Nine of the eleven editing events result in amino acid changes . Some of these RNA editing sites ar"
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    • "A-to-I RNA editing plays an essential role in brain development in both Drosophila and mammals [16]–[18]. In Drosophila, several genes involved in synaptic vesicle release machinery are targets of the dADAR enzyme (e.g. "
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    • "A-to-I editing in Drosophila is catalyzed by a single neurally enriched enzyme, ADAR, which plays an important role in the maintenance of neuronal homeostasis (30–32). Consistent with this physiological role, adar mutant adults display numerous behavioral defects as well as age-dependent neurodegeneration (33,34). The expression levels of the adar transcript increased during metamorphosis (Figure 1B), suggesting a developmental basis for these defects, and coincided with the onset of the let-7-C transcript (Figure 1C), a locus required for the formation of the adult nervous system (23,25,29). "
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