RNA editing regulates transposon-mediated heterochromatic gene silencing

Yiannis A. Savva, James E. C. Jepson, Yao-Jen Chang, Rachel Whitaker, Brian C. Jones, Georges St Laurent, Michael R. Tackett, Philipp Kapranov, Nan Jiang, Guyu Du, Stephen L. Helfand and Robert A. Reenan ()
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Yiannis A. Savva: Cell Biology and Biochemistry, Brown University
James E. C. Jepson: Cell Biology and Biochemistry, Brown University
Yao-Jen Chang: Cell Biology and Biochemistry, Brown University
Rachel Whitaker: Cell Biology and Biochemistry, Brown University
Brian C. Jones: Cell Biology and Biochemistry, Brown University
Georges St Laurent: Cell Biology and Biochemistry, Brown University
Michael R. Tackett: St Laurent Institute, One Kendall Square
Philipp Kapranov: St Laurent Institute, One Kendall Square
Nan Jiang: Cell Biology and Biochemistry, Brown University
Guyu Du: Cell Biology and Biochemistry, Brown University
Stephen L. Helfand: Cell Biology and Biochemistry, Brown University
Robert A. Reenan: Cell Biology and Biochemistry, Brown University

Nature Communications, 2013, vol. 4, issue 1, 1-11

Abstract: 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.

Date: 2013
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DOI: 10.1038/ncomms3745

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