Department of Molecular Biology, Cell Biology and Biochemistry, Brown University, 185 Meeting Street, Providence, Rhode Island 02912, USA.
Nat Commun. 2013;4:2745. doi: 10.1038/ncomms3745.
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.
异染色质形成驱动与沉默基因表达相关的表观遗传机制。抑制性异染色质是通过 RNA 干扰途径建立的，该途径由双链 RNA（dsRNAs）触发，dsRNAs 可以通过 RNA 编辑进行修饰。然而，这种修饰的生物学后果仍然是个谜。在这里，我们表明 RNA 编辑调节果蝇中的异染色质基因沉默。我们利用 RNA 编辑酶的结合活性来可视化由 Hoppel 转座元件介导的长 dsRNA 触发物的体内产生。通过同源重组，我们删除了这个触发物，这显著改变了异染色质基因沉默和染色质结构。此外，我们表明触发 RNA 被编辑，并且 dADAR 作为染色质状态的关键调节剂。此外，dADAR 自动编辑产生了一种基因沉默的天然抑制剂。最后，RNA 编辑活性的系统差异在一个群体内产生了沉默状态的个体间变异。我们的数据揭示了 RNA 编辑在调节基因表达方面的全局作用。
