Genetic characterization of the mRNAs encoding alpha-bungarotoxin: isoforms and RNA editing in Bungarus multicinctus gland cells

The mRNA encoding alpha-bungarotoxin (alpha-Butx) was prepared from the ven om glands of Bungarus multicinctus by Cap-finder cDNA synthesis. The sequen ces of the 3'- and 5'-flanking regions including a signal peptide of alpha- Butx were almost identical with those of Elapidae and Hydrophiidae toxins, suggesting that they may have the same origin. Sixteen polymorphic mRNA seq uences of alpha-Butx were detected from B. multicinctus gland cells. Analys is of the genomic DNA of alpha-Butx indicated that the polymorphic mRNA ori ginated from one DNA sequence, Most of the mutations in alpha-Butx mRNA wer e silent and the hot-spot variations occurred at 78, 107, 129, 198 and 201 nt in alpha-Butx mRNA, Ten distinct protein sequences of alpha-Butx could b e deduced from the polymorphic mRNA and one of the isoforms has already bee n isolated. Since alpha-Butx DNA is a single copy in the genome, the RNA po lymorphism might result from post-transcriptional editing. These results in dicate that the authentic alpha-Butx is in fact derived from edited mRNAs, RNA editing may contribute a common mechanism toward the diversity of alpha -neurotoxins in snake glands.