The organization of the genes encoding the A chains of beta-bungarotoxins: evidence for the skipping of exon.

Bungarus multicinctus (Taiwan banded krait) beta-bungarotoxins consist of two dissimilar polypeptide chains, A and B. The A chain is structurally homologous to phospholipase A(2) (PLA(2)) enzymes. The structural organization of the genes encoding A1, A2 and A8 chains are reported in this study. Their nucleotide sequences shared up to 97.5% identity. Alignment of the determined A chain genes with their cDNAs revealed that A1 chain gene organized with four exons and three introns, while A2 chain gene comprised three exons and two introns. When A2 chain is expressed, the region corresponding to the first exon of A1 chain gene is skipped instead of the inclusion of intronic sequence adjacent to the second exon. The resulting A2 chain mRNA encoded a 25 residue signal peptide, which is different from A1 chain mRNA with a 27 residue signal peptide. Nevertheless, expression of the A chain genes was partly regulated by a common mechanism as evidenced by sequence conservation of their promoter region and consensus transcriptional factor binding-sites inside this region. 5'-RACE analyses revealed that A chain mRNAs with 27 residue signal peptide represented the predominant species in the preparation of B. multicinctus venom gland mRNAs. Comparative analyses on PLA(2) genes and cDNAs suggest that this is the first report on the skipping of exon which changes the signal peptide sequence of snake venom proteins.