Publication details
Editing-independent effects of Drosophila Adar on heterochromatin silencing
| Authors | |
|---|---|
| Year of publication | 2026 |
| Type | Peer-reviewed scientific article |
| Magazine / Source | RNA |
| MU Faculty or unit | |
| Citation | |
| web | https://rnajournal.cshlp.org/content/32/6/962 |
| Doi | https://doi.org/10.1261/rna.080873.125 |
| Keywords | ADAR; RNA editing; heterochromatin silencing; ecdysone |
| Description | ADAR RNA editing enzymes deaminate selected adenosines to inosines in dsRNA. In Drosophila, inosine in dsRNA inhibits cleavage by Dcr2, and some ADAR proteins contribute an additional, editing-independent inhibition. The Drosophila AdarG isoform, in particular, has been proposed to inhibit HP1-mediated heterochromatin silencing of repetitive sequences initiated by specific dsRNAs. To address the functions of AdarG, we overexpressed it from new UAS-Adar lines, under the control of a temperature-regulated Act5C(ts)-GAL4 driver. Overexpression of the adult AdarG isoform or catalytically inactive AdarE374A led to larval lethality with some escaper pupae that show an ecdysone-related, head eversion defect. This indicates an editing-independent effect of high Adar expression. Pupae show aberrantly elevated innate immune and early ecdysone gene transcript expression, and no flies eclose. RNAi knockdown of ecdysone receptor A (EcRA) or increased expression of the histone H3K9me2,3-associated HP1 protein partially rescues AdarG overexpression defects and normalizes gene expression in rescued progeny flies. In other reports, Drosophila mutants with reduced HP1, or egg (SetDB1), Su(var)3-9 double mutants with reduced histone H3K9me2,3 also produce larvae with ecdysone-related and innate immune defects. We show that overexpressed AdarG inhibits histone H3K9me-mediated epigenetic silencing through an editing-independent effect, most likely at the dsRNA/Dcr2/Ago2 initiation stage. |
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