title: Auto-regulatory RNA editing fine-tunes mRNA re-coding and complex behaviour in Drosophila.
abstract: Auto-regulatory feedback loops are a common molecular strategy used to optimize protein function. In Drosophila, many messenger RNAs involved in neuro-transmission are re-coded at the RNA level by the RNA-editing enzyme, dADAR, leading to the incorporation of amino acids that are not directly encoded by the genome. dADAR also re-codes its own transcript, but the consequences of this auto-regulation in vivo are unclear. Here we show that hard-wiring or abolishing endogenous dADAR auto-regulation dramatically remodels the landscape of re-coding events in a site-specific manner. These molecular phenotypes correlate with altered localization of dADAR within the nuclear compartment. Furthermore, auto-editing exhibits sexually dimorphic patterns of spatial regulation and can be modified by abiotic environmental factors. Finally, we demonstrate that modifying dAdar auto-editing affects adaptive complex behaviours. Our results reveal the in vivo relevance of auto-regulatory control over post-transcriptional mRNA re-coding events in fine-tuning brain function and organismal behaviour.
authors.affiliation: Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, Rhode Island 02912, USA.
authors.forename: Yiannis A
authors.initials: YA
authors.lastname: Savva
authors.forename: James E C
authors.initials: JE
authors.lastname: Jepson
authors.forename: Asli
authors.initials: A
authors.lastname: Sahin
authors.forename: Arthur U
authors.initials: AU
authors.lastname: Sugden
authors.forename: Jacquelyn S
authors.initials: JS
authors.lastname: Dorsky
authors.forename: Lauren
authors.initials: L
authors.lastname: Alpert
authors.forename: Charles
authors.initials: C
authors.lastname: Lawrence
authors.forename: Robert A
authors.initials: RA
authors.lastname: Reenan
mesh_terms: D000243:Adenosine Deaminase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology / Q000235:genetics; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics*; D005786:Gene Expression Regulation; D006706:Homeostasis; D008297:Male; D008969:Molecular Sequence Data; D017393:RNA Editing; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins; D016415:Sequence Alignment
chemical_list: D029721:Drosophila Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase