Aspartyl beta-hydroxylase (Asph) and an evolutionarily conserved isoform of Asph missing the catalytic domain share exons with junctin

The mouse aspartyl beta -hydroxylase gene (Asph, BAH) has been cloned and c haracterized, The mouse BAH gene spans 200 kilobase pairs of genomic DNA an d contains 24 exons. Of three major BAH-related transcripts, the two larges t (6,629 and 4,419 base pairs) encode full-length protein and differ only i n the use of alternative polyadenylation signals. The smallest BAH-related transcript (2,789 base pairs) uses an alternative 3' terminal exon, resulti ng in a protein lacking a catalytic domain. Evolutionary conservation of th is noncatalytic isoform of BAH (humbug) is demonstrated in mouse, man, and Drosophila, Monoclonal antibody reagents were generated, epitope-mapped, an d used to definitively correlate RNA bands on Northern blots with protein s pecies on Western blots, The gene for mouse junctin, a calsequestrin-bindin g protein, was cloned and characterized and shown to be encoded from the sa me locus, When expressed in heart tissue, BAH/humbug; preferably use the fi rst exon and often the fourth exon of junctin while preserving the reading frame. Thus, three individual genes share common exons and open reading fra mes and use separate promoters to achieve differential expression, splicing , and function in a variety of tissues, This unusual form of exon sharing s uggests that the functions of junctin, BAH, and humbug may be linked.