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Science 301 (5634): 832-836

Copyright © 2003 by the American Association for the Advancement of Science

Nervous System Targets of RNA Editing Identified by Comparative Genomics

Barry Hoopengardner,* Tarun Bhalla,* Cynthia Staber, Robert Reenan{dagger}

Abstract: An unknown number of precursor messenger RNAs undergo genetic recoding by modification of adenosine to inosine, a reaction catalyzed by the adenosine deaminases acting on RNA (ADARs). Discovery of these edited transcripts has always been serendipitous. Using comparative genomics, we identified a phylogenetic signature of RNA editing. We report the identification and experimental verification of 16 previously unknown ADAR target genes in the fruit fly Drosophila and one in humans—more than the sum total previously reported. All of these genes are involved in rapid electrical and chemical neurotransmission, and many of the edited sites recode conserved and functionally important amino acids. These results point to a pivotal role for RNA editing in nervous system function.

Department of Genetics and Developmental Biology, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA.

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* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: rreenan{at}neuron.uchc.edu

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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
Effects of Length and Location on the Cellular Response to Double-Stranded RNA.
Q. Wang and G. G. Carmichael (2004)
Microbiol. Mol. Biol. Rev. 68, 432-452
   Abstract »    Full Text »    PDF »
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A. T. Kho, Q. Zhao, Z. Cai, A. J. Butte, J. Y.H. Kim, S. L. Pomeroy, D. H. Rowitch, and I. S. Kohane (2004)
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   Abstract »    Full Text »    PDF »
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