Auto-regulatory RnA editing fine-tunes mRnAre-coding and complex behaviour in Drosophila

摘要

Auto-regulatory feedback loops are a common molecular strategy used to optimize proteinfunction. In Drosophila, many messenger RnAs involved in neuro-transmission are re-codedat the RnA level by the RnA-editing enzyme, dADAR, leading to the incorporation of aminoacids that are not directly encoded by the genome. dADAR also re-codes its own transcript,but the consequences of this auto-regulation in vivo are unclear. Here we show that hardwiring or abolishing endogenous dADAR auto-regulation dramatically remodels the landscapeof re-coding events in a site-specific manner. These molecular phenotypes correlate withaltered localization of dADAR within the nuclear compartment. Furthermore, auto-editingexhibits sexually dimorphic patterns of spatial regulation and can be modified by abioticenvironmental factors. Finally, we demonstrate that modifying dAdar auto-editing affectsadaptive complex behaviours. our results reveal the in vivo relevance of auto-regulatory controlover post-transcriptional mRnA re-coding events in fine-tuning brain function and organismalbehaviour.