Human dopamine β-hydroxylase gene: two mRNA types having different 3'terminal regions are produced through alternative polyadenylation

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Abstract
Two kinds of cDNA (types A and B) encoding human dopamine β-hydroxylase (DBH) were isolated from a pheochromocytoma cDNA library. Type A (2.7 kb) and B (2.4 kb) encoded the same amino acid sequence and were different only in 3'-untranslated region. Type A contained 3'-extension of 300 by at the end of type B. Subsequently, we isolated human DBH gene and analyzed genonic DNA by Southern hybridization. Human DBH gene (approximately 23 kb) was composed of 12 exons and existed as a single gene on genone. Exon 12 encoded 3'-terminal region of 1, 013 by of type A, including the 300 by sequence. These results indicate that alternative use of two polyadenylation sites from a single DBH gene generates different nRNA types. This conclusion was supported by Northern hybridization and S1 nuclease mapping experiments. The ratio of type A and B mRNAs in pheochromocytona was roughly 1.0 to 0.2. We found possible transcription regulatory elements, TATA, CCAAT, CACCC, GC boxes, near the transcription initiation site of DBH gene. Sequences homologous to glucocorticoid and cyclic AMP response elements were also observed.