RNA EDITING OF BRAIN GLUTAMATE-RECEPTOR CHANNELS - MECHANISM AND PHYSIOLOGY

Glutamate-gated cation selective channels mediate fast excitatory neur otransmission in the mammalian brain. Functionally critical channel po sitions contain amino acid residues not predicted from the exonic sequ ence for the channel subunits. The codons for these residues are creat ed in the respective primary gene transcripts by the site selective de amination of adenosine to inosine. This type of RNA editing requires a short double-stranded RNA structure formed by the exonic sequence aro und the adenosine targeted for deamination with a complementary sequen ce in the downstream intron and hence, it precedes splicing. Candidate enzymes for nuclear transcript editing currently comprise three molec ularly cloned mammalian RNA-dependent adenosine deaminases. Two of the se are expressed in most body tissues, perhaps indicating that adenosi ne deamination in transcripts is more global than has been recognized. Indeed, numerous mRNAs in different tissues may contain inosine resid ues and encode proteins with amino acid substitutions and different pr operties relative to the exonically encoded forms. If so, RNA editing by adenosine deamination may significantly enlarge the functional repe rtoire of the mammalian genome. (C) 1998 Elsevier Science B.V. All rig hts reserved.