Auto-regulatory RNA editing fine-tunes mRNA re-coding and complex behaviour in Drosophila

Yiannis A. Savva, James E.C Jepson, Asli Sahin, Arthur U. Sugden, Jacquelyn S. Dorsky, Lauren Alpert, Charles Lawrence 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
Asli Sahin: Cell Biology and Biochemistry, Brown University
Arthur U. Sugden: Cell Biology and Biochemistry, Brown University
Jacquelyn S. Dorsky: Cell Biology and Biochemistry, Brown University
Lauren Alpert: Brown University
Charles Lawrence: Brown University
Robert A. Reenan: Cell Biology and Biochemistry, Brown University

Nature Communications, 2012, vol. 3, issue 1, 1-10

Abstract: Abstract Auto-regulatory feedback loops are a common molecular strategy used to optimize protein function. In Drosophila, many messenger RNAs involved in neuro-transmission are re-coded at the RNA level by the RNA-editing enzyme, dADAR, leading to the incorporation of amino acids 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 hard-wiring or abolishing endogenous dADAR auto-regulation dramatically remodels the landscape of re-coding events in a site-specific manner. These molecular phenotypes correlate with altered localization of dADAR within the nuclear compartment. Furthermore, auto-editing exhibits sexually dimorphic patterns of spatial regulation and can be modified by abiotic environmental factors. Finally, we demonstrate that modifying dAdar auto-editing affects adaptive complex behaviours. Our results reveal the in vivo relevance of auto-regulatory control over post-transcriptional mRNA re-coding events in fine-tuning brain function and organismal behaviour.

Date: 2012
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DOI: 10.1038/ncomms1789

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