J. Biochem, 1988, Vol. 103, No. 6 907-912
© 1988 Japanese Biochemical Society
research-article |
Structure of the Human Tyrosine Hydroxylase Gene: Alternative Splicing from a Single Gene Accounts for Generation of Four mRNA Types1
* Department of Biochemistry, Nagoya University School of Medicine Showa-ku, Nagoya, Aichi 466
** Department of Biochemistry, Yamaguchi University School of Medicine Ube, Yamaguchi 755
*** Institute for Comprehensive Medical Science, Fujita-Gakuen Health University School of Medicine Toyoake, Aichi 470-11
2To whom correspondence should be addressed.
Tyrosine hydroxylase (TH) is a rate-limiting enzyme for catecholamine biosynthesis. Recently, Grima et al. (Nature (1987) 326, 707–711) and we (Biochem. Biophys. Res. Commun. (1987) 146, 971–975; Nucleic Acids Res. (1987) 15, 6733) reported four similar but distinct mRNAs that encode human TH. These mRNAs are constant for the major part, but are distinguishable from one another as to the insertion/deletion of 12-bp and 81-bp sequences near the N-terminus. We isolated genomic clones encoding the human TH gene and determined the nucleotide sequence. The human TH gene is split into 14 exons. The 12-bp insertion sequence is encoded by the 3'-terminal portion of the first exon. The 81-bp insertion sequence corresponds to the second exon. Taking into consideration also the results of Southern blot analysis of human genomic DNA, we concluded that the four types of human TH mRNA are produced through alternative splicing from a single gene. Two kinds of alternative splicing are involved: the alternative use of two donor sites in the first exon, and the inclusion/exclusion of the second exon. We propose a possible secondary structure for the latter alternative splicing pathway.
1This work was supported by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science and Culture of Japan.
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