HUMAN GAMMA-AMINOBUTYRIC ACID-TYPE-A RECEPTOR ALPHA-5 SUBUNIT GENE (GABRA5) - CHARACTERIZATION AND STRUCTURAL ORGANIZATION OF THE 5'-FLANKING REGION

The gamma-aminobutyric acid-type A receptor alpha 5 subunit gene (GABR A5) is widely expressed in brain and localized to the imprinted human chromosome 15q11-q13. A combination of cDNA library screening and 5' R ACE analysis led to identification of three distinct mRNA isoforms of GABRA5 in human adult and fetal brain tissues, each of which differs o nly in the noncoding 5' UTR sequence. Alignment of the genomic and cDN A sequences of GABRA5 revealed that the mRNA isoforms resulted from th ree alternative first exons 1A, 1B, and 1C. Northern blot analysis sho wed that, the expression of GABRA5 was not only tissue specific but re gion specific in brain, CAT reporter assays revealed promoter elements in the 5' proximity of each first exon. The GABRA5 promoter regions l acked TATA and CCAAT bares but contained several other consensus trans criptional factor recognition sequences, These findings suggest that t he differential exon 1 usage of GABRA5 arises as a consequence of alte rnative promoter activation. (C) 1997 Academic Press.