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PMID: 24201902 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

RNA editing regulates transposon-mediated heterochromatic gene silencing.

Nature communications ·Vol. 4 ·2013-00-00 ·Pages 2745

Savva YA, Jepson JE, Chang YJ, Whitaker R, Jones BC, St Laurent G, Tackett MR, Kapranov P, Jiang N, Du G, Helfand SL, Reenan RA

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.

MeSH Terms
Adenosine Deaminase/genetics,metabolism Animals DNA Transposable Elements/genetics,physiology Drosophila Proteins/genetics,metabolism Drosophila melanogaster/genetics,metabolism Gene Silencing Heterochromatin/genetics Protein Binding RNA Editing/genetics,physiology RNA, Double-Stranded/genetics,metabolism
Chemicals
DNA Transposable Elements Drosophila Proteins Heterochromatin RNA, Double-Stranded Adar protein, Drosophila Adenosine Deaminase
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Savva Yiannis A
Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, 185 Meeting Street, Providence, Rhode Island 02912, USA.
Jepson James E C
Chang Yao-Jen
Whitaker Rachel
Jones Brian C
St Laurent Georges
Tackett Michael R
Kapranov Philipp
Jiang Nan
Du Guyu
Helfand Stephen L
Reenan Robert A
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Article Info
Journal
Nature communications
Abbr.
Nat Commun
ISSN
2041-1723
DOI
10.1038/ncomms3745
Published
2013-00-00
Pages
2745
Language
English
Region
England
NLM ID
101528555
PMCID
PMC3992701
Subset
IM
Grants
NIA NIH HHS · AG24353 · United States
NIA NIH HHS · R01 AG025277 · United States
NIGMS NIH HHS · T32 GM007601 · United States
NIA NIH HHS · R01 AG024353 · United States
NIA NIH HHS · R37 AG016667 · United States
NIA NIH HHS · RF1 AG024353 · United States
NIA NIH HHS · T32 AG041688 · United States
NIA NIH HHS · AG16667 · United States
NIA NIH HHS · AG25277 · United States
NIA NIH HHS · R01 AG016667 · United States
External Links
PubMed source DOI: 10.1038/ncomms3745 PMC Full Text View journal details
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