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Alternative splicing in the human cytochrome P450HB6 gene is the probable mechanism for the generation of a high level of aberrant messages in which intron 5 is retained and exon 8 is missing, or in which exon 8 is replaced by a cryptic exon (exon 8A) derived from intron 8 (1). A further variant human P450IIB mRNA (cDNA) has been isolated (hIIB2; (2)) in which the first 29 nucleotides of exon 4 are replaced by 44 nucleotides of unknown origin. We have sequenced more of the P450IIB6 gene (XMP11; (1)) and show that these 44 bp are present within intron 3. Analysis of the sequence surrounding the 44-bp segment shows that the 5' and 3' flanking sequences match well with the splice acceptor and donor site consensuses (YnNCAGG; NAGGTRAGT). A splice acceptor site is present within exon 4 (positions 18 — 33) whose use would lead to the removal of the first 29 nucleotides. These data suggest that the variant mRNA (cDNA) hIIB2 could be generated by alternative splicing of P450IIB6 pre-mRNA in which the 44-bp segment within intron 3 acts as a cryptic exon (exon 3A) and is used in conjunction with splice acceptor site within exon 4.

Alternative splicing in the human cytochrome P450IIB6 gene: use of a cryptic exon within intron 3 and splice acceptor site within exon 4