title: RNA editing regulates transposon-mediated heterochromatic gene silencing.
abstract: Heterochromatin formation drives epigenetic mechanisms associated with silenced gene expression. Repressive heterochromatin is established through the RNA interference pathway, triggered by double-stranded RNAs (dsRNAs) that can be modified via RNA editing. However, the biological consequences of such modifications remain enigmatic. Here we show that RNA editing regulates heterochromatic gene silencing in Drosophila. We utilize the binding activity of an RNA-editing enzyme to visualize the in vivo production of a long dsRNA trigger mediated by Hoppel transposable elements. Using homologous recombination, we delete this trigger, dramatically altering heterochromatic gene silencing and chromatin architecture. Furthermore, we show that the trigger RNA is edited and that dADAR serves as a key regulator of chromatin state. Additionally, dADAR auto-editing generates a natural suppressor of gene silencing. Lastly, systemic differences in RNA editing activity generates interindividual variation in silencing state within a population. Our data reveal a global role for RNA editing in regulating gene expression.
authors.affiliation: Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, 185 Meeting Street, 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: Yao-Jen
authors.initials: YJ
authors.lastname: Chang
authors.forename: Rachel
authors.initials: R
authors.lastname: Whitaker
authors.forename: Brian C
authors.initials: BC
authors.lastname: Jones
authors.forename: Georges
authors.initials: G
authors.lastname: St Laurent
authors.forename: Michael R
authors.initials: MR
authors.lastname: Tackett
authors.forename: Philipp
authors.initials: P
authors.lastname: Kapranov
authors.forename: Nan
authors.initials: N
authors.lastname: Jiang
authors.forename: Guyu
authors.initials: G
authors.lastname: Du
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Helfand
authors.forename: Robert A
authors.initials: RA
authors.lastname: Reenan
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004251:DNA Transposable Elements / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D020868:Gene Silencing; D006570:Heterochromatin / Q000235:genetics*; D011485:Protein Binding; D017393:RNA Editing / Q000235:genetics / Q000502:physiology*; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism
chemical_list: D004251:DNA Transposable Elements; D029721:Drosophila Proteins; D006570:Heterochromatin; D012330:RNA, Double-Stranded; C567956:Adar protein, Drosophila; D000243:Adenosine Deaminase