CLONING OF A HUMAN RNA EDITING DEAMINASE (ADARB1) OF GLUTAMATE RECEPTORS THAT MAPS TO CHROMOSOME 21Q22.3

RED1 is a double-stranded RNA-specific editase characterized in the ra t and is implicated in the editing of glutamate receptor subunit pre-m RNAs, particularly in the brain. Starting from human ESTs homologous t o the rat RED1 sequence, we have characterized two forms of human RED1 cDNAs, one form coding for a putative peptide of 701 amino acids (sim ilar to the shorter of two rat mRNAs) and a long form coding for a put ative protein of 741 amino acids, the extra 120 bp of which are homolo gous to an AluJ sequence. Both forms were observed at approximately eq ual levels in cDNA clones and in seven different human tissues tested by RT-PCR The human and rat short isoforms have 95 and 85% sequence id entity at the amino acid and nucleotide levels, respectively. The huma n sequence (designated ADARB1 by the HGMW Nomenclature Committee) cont ains two double stranded RNA-binding domains and a deaminase domain im plicated in its editing action. Northern blot analysis detected two tr anscripts of 8.8 and 4.2 kb strongly expressed in brain and in many hu man adult and fetal tissues. ADARB1 maps to human chromosome 21q22.3, a region to which several genetic disorders map, including one form of bipolar affective disorder. Recently it was shown that heterozygous m ice harboring an editing-incompetent glutamate receptor B allele have early onset fatal epilepsy. Since glutamate receptor channels are esse ntial elements in synaptic function and plasticity and mediate patholo gy in many neurological disorders, and since RED1 is central in glutam ate receptor channel control, ADARB1 is a candidate gene for diseases with neurological symptoms, such as bipolarlar affective disorder and epilepsy. (C) 1997 Academic Press.