Splice-Variant- and Stage-Specific RNA Editing of the Drosophila GABA Receptor Modulates Agonist Potency

• Published in: The Journal of neuroscience 2009-04, Vol.29 (13), p.4287-4292
• Main Authors: Jones, Andrew K, Buckingham, Steven D, Papadaki, Magdalini, Yokota, Maiko, Sattelle, Benedict M, Matsuda, Kazuhiko, Sattelle, David B
• Format: Article
• Language: English
• Subjects: Age Factors; Alternative Splicing - genetics; Amino Acid Sequence; Analysis of Variance; Animals; Dose-Response Relationship, Drug; Drosophila melanogaster; Drosophila Proteins - genetics; Embryo, Nonmammalian; gamma-Aminobutyric Acid - pharmacology; Gene Expression - genetics; Gene Expression Regulation, Developmental - drug effects; Gene Expression Regulation, Developmental - genetics; Membrane Potentials - drug effects; Membrane Potentials - genetics; Membrane Potentials - physiology; Microinjections - methods; Mutation - physiology; Oocytes; Patch-Clamp Techniques; Receptors, GABA-A - genetics; RNA Editing - drug effects; RNA Editing - physiology; Xenopus laevis
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.5251-08.2009

The molecular diversity of many gene products functioning in the nervous system is enhanced by alternative splicing and adenosine-to-inosine editing of pre-mRNA. Using RDL, a Drosophila melanogaster GABA-gated ion channel, we examined the functional impact of RNA editing at several sites along with alternative splicing of more than one exon. We show that alternative splicing and RNA editing have a combined influence on the potency of the neurotransmitter GABA, and the editing isoforms detected in vivo span the entire functional range of potencies seen for all possible edit variants expressed in Xenopus laevis oocytes. The extent of RNA editing is developmentally regulated and can also be linked to the choice of alternative exons. These results provide insights into how the rich diversity of signaling necessary for complex brain function can be achieved by relatively few genes.