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The Journal of Neuroscience, April 1, 2009, 29(13):4287-4292; doi:10.1523/JNEUROSCI.5251-08.2009

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

Andrew K. Jones,¹ Steven D. Buckingham,¹ Magdalini Papadaki,¹ Maiko Yokota,² Benedict M. Sattelle,¹ Kazuhiko Matsuda,² and David B. Sattelle¹

¹Medical Research Council, Functional Genomics Unit, University of Oxford, Oxford OX1 3QX, United Kingdom, and ²Department of Applied Biological Chemistry, School of Agriculture, Kinki University, Nakamachi, Nara 631-8505, Japan

Correspondence should be addressed to David B. Sattelle, Medical Research Council, Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, South Parks Road, Oxford OX1 3QX, UK. Email: david.sattelle{at}dpag.ox.ac.uk

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.

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Received Oct. 31, 2008; revised Jan. 21, 2009; accepted Jan. 22, 2009.

Correspondence should be addressed to David B. Sattelle, Medical Research Council, Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, South Parks Road, Oxford OX1 3QX, UK. Email: david.sattelle{at}dpag.ox.ac.uk

This article has been cited by other articles:

				J. E. C. Jepson and R. A. Reenan Adenosine-to-Inosine Genetic Recoding Is Required in the Adult Stage Nervous System for Coordinated Behavior in Drosophila J. Biol. Chem., November 6, 2009; 284(45): 31391 - 31400. [Abstract] [Full Text] [PDF]

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