Isolation and Characterization of the Human Tyrosine Hydroxylase Gene: Identification of 5’ Alternative Splice Sites Responsible for Multiple mRNAs

Karen L. O’Malley, Michael J. Anhalt, Brian M. Martin, John R. Kelsoe, Susan L. Winfield, Edward I. Ginns

Research output: Contribution to journalArticlepeer-review

156 Scopus citations

Abstract

A full-length genomic clone for human tyrosine hydroxylase (L-tyrosine, tetrahydropteridine:oxygen oxidoreductase, EC 1.14.16.2) has been isolated. A human brain genomic library constructed in EMBL3 was screened by using a rat cDNA for tyrosine hydroxylase as a probe [Brown, E. R., Coker, G. T., III, & O’Malley, K. L. (1987) Biochemistry 26, 5208–5212]. Out of one million recombinant phage, one clone was identified that hybridized to both 5’ and 3’ rat cDNA probes. Restriction endonuclease mapping, Southern blotting, and sequence analysis revealed that, like its rodent counterpart, the human gene is single copy, contains 13 primary exons, and spans approximately 8 kilobases (kb). In contrast to the rat gene, human tyrosine hydroxylase undergoes alternative RNA processing within intron 1, generating at least three distinct mRNAs. A comparison of the human tyrosine hydroxylase and phenylalanine hydroxylase [DiLella, A. G., Kwok, S. C. M., Ledley, F. D., Marvit, J., & Woo, S. L. C. (1986) Biochemistry 25, 743–749] genes indicates that although both probably evolved from a common ancestral gene, major changes in the size of introns have occurred since their divergence.

Original languageEnglish
Pages (from-to)6910-6914
Number of pages5
JournalBiochemistry
Volume26
Issue number22
DOIs
StatePublished - 1987

Fingerprint

Dive into the research topics of 'Isolation and Characterization of the Human Tyrosine Hydroxylase Gene: Identification of 5’ Alternative Splice Sites Responsible for Multiple mRNAs'. Together they form a unique fingerprint.

Cite this