title: Tuning of RNA editing by ADAR is required in Drosophila.
abstract: RNA editing increases during development in more than 20 transcripts encoding proteins involved in rapid synaptic neurotransmission in Drosophila central nervous system and muscle. Adar (adenosine deaminase acting on RNA) mutant flies expressing only genome-encoded, unedited isoforms of ion-channel subunits are viable but show severe locomotion defects. The Adar transcript itself is edited in adult wild-type flies to generate an isoform with a serine to glycine substitution close to the ADAR active site. We show that editing restricts ADAR function since the edited isoform of ADAR is less active in vitro and in vivo than the genome-encoded, unedited isoform. Ubiquitous expression in embryos and larvae of an Adar transcript that is resistant to editing is lethal. Expression of this transcript in embryonic muscle is also lethal, with above-normal, adult-like levels of editing at sites in a transcript encoding a muscle voltage-gated calcium channel.
authors.affiliation: MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK.
authors.forename: Liam P
authors.initials: LP
authors.lastname: Keegan
authors.forename: James
authors.initials: J
authors.lastname: Brindle
authors.forename: Angela
authors.initials: A
authors.lastname: Gallo
authors.forename: Anne
authors.initials: A
authors.lastname: Leroy
authors.forename: Robert A
authors.initials: RA
authors.lastname: Reenan
authors.forename: Mary A
authors.initials: MA
authors.lastname: O'Connell
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D015220:Calcium Channels / Q000096:biosynthesis / Q000235:genetics; D004330:Drosophila / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000201:enzymology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007814:Larva / Q000235:genetics / Q000378:metabolism; D009132:Muscles / Q000201:enzymology / Q000378:metabolism; D009928:Organ Specificity; D017433:Protein Structure, Secondary; D012313:RNA / Q000378:metabolism*; D017393:RNA Editing / Q000502:physiology*; D016601:RNA-Binding Proteins
chemical_list: D015220:Calcium Channels; D029721:Drosophila Proteins; D007527:Isoenzymes; D016601:RNA-Binding Proteins; C472405:cac protein, Drosophila; D012313:RNA; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase