STRUCTURE OF THE HUMAN GENE AND 2 RAT CDNAS ENCODING THE ALPHA-CHAIN OF GTP-BINDING REGULATORY PROTEIN-GO - 2 DIFFERENT MESSENGER-RNAS ARE GENERATED BY ALTERNATIVE SPLICING

G(O) is a specific class ("other") of signal-transducing heterotrimeric GTP-binding proteins (G proteins) that is expressed in high levels in mammalian brain. We have cloned two different rat cDNAs encoding the alpha-subunit of G(O) (G(O)-alpha-1 and G(O)-alpha-2) and a human G(O)-alpha chromosomal gene. The human G(O)-alpha gene spans more than 100 kilobases and contains 11 exons, including one noncoding exon in the 3' flanking region. The 5' flanking region is highly G + C-rich and contains five G.C boxes (Sp1 binding sites) but no TATA box. Exons 7 and 8 coding for amino acid residues 242-354 of G(O)-alpha protein are duplicated (referred to as exons 7A, 7B, 8A, and 8B). It was found that exons 7A and 8A code for G(O)-alpha-1, and 7B and 8B code for G(O)-alpha-2. This indicates that two different G(O)-alpha mRNAs may be generated by alternative splicing of a single G(O)-alpha gene. The splice sites of the G(O)-alpha-1 and G(O)-alpha-2 genes are completely identical with those encoding human inhibitory G protein alpha-subunits G(i)2-alpha and G(i)3-alpha [Itoh, H., Toyama, R., Kozasa, T., Tsukamoto, T., Matsuoka, M. & Kaziro, Y. (1988) J. Biol. Chem. 263, 6656-6664] and also transducin G protein alpha-subunit G(t)1-alpha [Raport, C. J., Dere, B. & Hurley, J. (1989) J. Biol. Chem. 264, 7122-7128]. Sequence homology and conservation of the exon-intron organization indicate that the genes coding for G(O)-alpha, G(i)2-alpha, G(i)3-alpha, G(t)1-alpha, and probably G(i)1-alpha may be evolved from a common progenitor. Like G(O)-alpha-1, G(O)-alpha-2 is expressed mainly in brain.