Journal of Biological Chemistry
Volume 270, Issue 8, 24 February 1995, Pages 3748-3756
Journal home page for Journal of Biological Chemistry

Nucleic Acids, Protein Synthesis, and Molecular Genetics
The Human Tryptophan Hydroxylase Gene: AN UNUSUAL SPLICING COMPLEXITY IN THE 5′-UNTRANSLATED REGION (∗)

https://doi.org/10.1074/jbc.270.8.3748Get rights and content
Under a Creative Commons license
open access

We report the isolation and the organization of the gene encoding human tryptophan hydroxylase (TPH) and an analysis of the corresponding mRNAs. The gene spans a region of 29 kilobases, which contains at least 11 exons and a variably spliced 5′-untranslated region (5′-UTR). The sequence of the coding region and the majority of the positions of the intron-exon boundaries of human TPH gene are very similar to those encoding human tyrosine hydroxylase and phenylalanine hydroxylase, the other members of the aromatic amino acid hydroxylase family. Phylogenetic analysis evidences the early divergence and the independent evolution of the three hydroxylase types. TPH cDNA cloning and anchored polymerase chain reaction revealed a diversity of the TPH mRNA, which is restricted to the 5′-UTR. Four TPH mRNA species were detected by Northern blot with pineal gland and carcinoid tumor RNAs. These messengers are transcribed from a single transcriptional initiation site, and their diversity results from differential splicing of three intron-like regions and of three exons located in the 5′-UTR. Analysis by S1 nuclease protection revealed that the intron-like regions in the 5′-UTR are mostly unspliced and that TPH mRNA species where the three intron-like regions are eliminated are present at low level in pineal gland and not detectable in carcinoid tumors.

Cited by (0)

This work was supported by grants from the Centre National de la Recherche Scientifique, the Institut National de la Santé et de la Recherche Medicale, the Association pour la Recherche contre le Cancer, the Institut de Recherche sur la Moëlle Epiniere and Rhône-Poulenc-Rorer. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank(TM)/EMBL Data Bank with accession number(s) X83213.

Supported by fellowships from the Institut de Recherche sur la Moëlle Epiniere.