Towards an Understanding of Integrative Brain Functions

RNA editing of brain glutamate receptor channels: mechanism and physiology

Peter H. Seeburg*, Miyoko Higuchi, Rolf Sprengel
Max-Planck Institute for Medical Research, Department of Molecular Neuroscience, Jahnstr. 29, 69120 Heidelberg, Germany

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Abstract
Glutamate-gated cation selective channels mediate fast excitatory neurotansmission in the mammalian brain. Functionally critical channel positions contain amino acid residues not predicted from the exonic sequence for the channel subunits. The codons for these residues are created in the respective primary gene transcripts by the site selective deamination of adinosine to inosine. This type of RNA editing requires a short double-stranded RNA structure formed by the exonic sequence around the adenosine targeted for deamination with a complementary sequence in the downstream intron and hence, it precedes splicing. Candidate enzymes for nuclear transcript editing currently comprise three molecularly cloned mammalian RNA-dependent adenosine deaminases. Two of these are expressed in most body tissues, perhaps indicating that adenosine deamination in transcripts is more global than has been recognized. Indeed, numerous mRNAs in different tissues may contain inosine residues and encode proteins with amino acid substitutions and different properties relative to the exonically encoded forms. If so, RNA editing by adenosine deamination may significantly enlarge the functional repertoire of the mammalian genome.

*Corresponding author: seeburg@mpimf-heidelberg.mpg.de

Brain Research Reviews 26 (1998) 217-229
Copyright © 1998 Elsevier Science B. V. All rights reserved.