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Zusammenfassung:
RED1 is a double-stranded RNA-specific editase characterized in the rat and is implicated in the editing of glutamate receptor subunit pre-mRNAs, particularly in the brain. Starting from human ESTs homologous to the rat RED1 sequence, we have characterized two forms of human RED1 cDNAs, one form coding for a putative peptide of 701 amino acids (similar to the shorter of two rat mRNAs) and a long form coding for a putative protein of 741 amino acids, the extra 120 bp of which are homologous to anAluJ sequence. Both forms were observed at approximately equal 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 identity at the amino acid and nucleotide levels, respectively. The human sequence (designated ADARB1 by the HGMW Nomenclature Committee) contains two double-stranded RNA-binding domains and a deaminase domain implicated in its editing action. Northern blot analysis detected two transcripts of 8.8 and 4.2 kb strongly expressed in brain and in many human 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 mice harboring an editing-incompetent glutamate receptor B allele have early onset fatal epilepsy. Since glutamate receptor channels are essential elements in synaptic function and plasticity and mediate pathology in many neurological disorders, and since RED1 is central in glutamate receptor channel control, ADARB1 is a candidate gene for diseases with neurological symptoms, such as bipolar affective disorder and epilepsy
