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

Nat Commun. 2012 Apr 24;3:790. doi: 10.1038/ncomms1789.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Deaminase / chemistry
  • Adenosine Deaminase / genetics*
  • Adenosine Deaminase / metabolism
  • Amino Acid Sequence
  • Animals
  • Cell Nucleus / enzymology
  • Cell Nucleus / genetics
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / chemistry
  • Drosophila melanogaster / enzymology*
  • Drosophila melanogaster / genetics*
  • Gene Expression Regulation
  • Homeostasis*
  • Male
  • Molecular Sequence Data
  • RNA Editing*
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins
  • Sequence Alignment

Substances

  • Drosophila Proteins
  • RNA, Messenger
  • RNA-Binding Proteins
  • ADARB1 protein, human
  • Adenosine Deaminase