A MAMMALIAN RNA EDITING ENZYME

EDITING of RNA(1) by site-selective adcnosine deamination alters codon s in brain-expressed pre-messenger RNAs for glutamate receptor (GluR) subunits(2-4) including a codon for a channel determinant (Q/R site) i n GluR-B, which controls the Ca2+ permeability of lpha-amino-3-hydroxy -5-methylisoxazole-4-propionic acid (AMPA) receptors(5,6). Editing of GluR pre-mRNAs requires a double-stranded RNA (dsRNA) structure formed by esonic and intronic sequences(4,7) and is catalysed by an unknown dsRNA adenosine deaminase. Here we report the cloning of complementary DNA for RED1, a dsRNA adenosine deaminase expressed in brain and peri pheral tissues that efficiently edits the Q/R site in GluR-B pre-mRNA in vitro. This site is poorly edited by DRADA, which is distantly sequ ence related to RED1. Both deaminases edit the R/G site in GluR-B pre- mRNA, indicating that members of an emerging gene family catalyse aden osine deamination in nuclear transcripts with distinct but overlapping substrate specificities.