Transcriptional and translational mechanisms of cytochrome b5 reductase isoenzyme generation in humans

Cytochrome b(5) reductase (b(5)R) is an essential enzyme that exists in soluble and membrane-bound isoforms, each with specific functions. In the rat, the two forms are generated from alternative transcripts differing in the first exons. In contrast, the biogenesis of b(5)R isoforms in the human is not yet well understood. In the present study we have detected three novel alternative exons, designated 1S, S' and 1B, located between the first alternative exon 1M and the common second exon in the human b(5)R gene. Accordingly, multiple M-type, S-type and SS'-type and B-type transcripts are generated. All types of human b(5)R transcript are expressed ubiquitously. An analysis of in vitro translation products demonstrated an alternative use of different AUG initiators resulting in the production of various human b(5)R protein isoforms. Our results indicate that the organization of the 5' region of the b(5)R gene is not conserved between rodents and humans. Insertion of Alu elements into the human b(5)R gene, in particular just upstream of the S/S' region, could be responsible for dynamic events of gene rearrangement during evolution.