Analysis of the 5’Region of the Human Tyrosine Hydroxylase Gene: Combinatorial Patterns of Exon Splicing Generate Multiple Regulated Tyrosine Hydroxylase Isoforms

  title={Analysis of the 5’Region of the Human Tyrosine Hydroxylase Gene: Combinatorial Patterns of Exon Splicing Generate Multiple Regulated Tyrosine Hydroxylase Isoforms},
  author={Beatrice Le Bourdell{\`e}s and Sylviane Boularand and Claudette Boni and Philippe Horellou and Sylvie Dumas and Brigitte Grima and J. Mallet},
  journal={Journal of Neurochemistry},
A single human gene has been described to encode multiple tyrosine hydroxylase (TH) mRNAs. The study of this variation has been extended by S1 mapping experiments and by analysis of the 5’region of the TH gene. Four different mRNAs were found to originate solely from alternative splicing of two exons. Comparison of the 5’flanking regions of human and rat genes discloses several highly conserved segments, likely to play an important role in the regulation of TH gene expression. 
Multiple Human Tyrosine Hydroxylase Enzymes, Generated Through Alternative Splicing, Have Different Specific Activities in Xenopus Oocytes
A significant difference in specific activity was found between each form of HTH, suggesting that alternative splicing may play a role in regulating HTH activity in vivo.
The human tyrosine hydroxylase gene
  • T. Nagatsu
  • Biology
    Cellular and Molecular Neurobiology
  • 2004
The results of Southern blot analysis and the nucleotide sequence of the human TH genomic DAN indicate that the four types of human TH mRNA are produced through alternative splicing from a single gene.
A Novel Rat Tyrosine Hydroxylase mRNA Species Generated by Alternative Splicing
Tyrosine hydroxylase catalyzes the first and rate‐limiting step in the biosynthesis of catecholamines, and alternative splicing of TH primary transcript has been described as a characteristic of higher primates and Drosophila.
Four Forms of Tyrosine Hydroxylase Are Present in Human Adrenal Medulla
All four of the predicted HTH protein forms were present in the adrenal glands from a diverse sample population, and electrophoretic transfers were developed with affinity‐purified rabbit anti‐HTH antibodies raised against peptides that reproduced the unique amino acid sequences predicted by the four mRNAHTH forms.
New Species of Human Tyrosine Hydroxylase mRNA Are Produced in Variable Amounts in Adrenal Medulla and Are Overexpressed in Progressive Supranuclear Palsy
The diversity of TH mRNAs is greater than previously described in the autonomous nervous system and new splice junctions corresponding to the skipping of exon 3 were identified by amplification of cDNA synthesized from pheochromocytoma RNA.
γ‐Aminobutyric AcidA Receptor Heterogeneity Is Increased by Alternative Splicing of a Novel β‐Subunit Gene Transcript
Analysis of the β4‐subunit gene reveals that the different transcripts encoding the two variants arise by the use of one of two 5′‐donor splice sites that are separated by 12 bp, which represents a further mechanism for the generation of GABAA receptor heterogeneity.


Identification and cell type specificity of the tyrosine hydroxylase gene promoter.
The initiation site for TH RNA synthesis is determined and the 5' end of the transcript is the same in several rat tissues in which TH is expressed as well as in rat pheochromocytoma cells (PC).
A single human gene encoding multiple tyrosine hydroxylases with different predicted functional characteristics
It is demonstrated that, in man, TH molecules are encoded by at least three distinct messenger RNAs, which could represent a novel means of regulating catecholamine levels in normal and pathological neurons.
Splice site selection in the proteolipid protein (PLP) gene transcript and primary structure of the DM-20 protein of central nervous system myelin.
This work isolated a copy of an alternatively spliced PLP gene transcript from a mouse brain cDNA library that was screened for PLP-related sequences and found that DM-20 mRNA results when a second 5' splice site, located 105 nucleotides within the third exon of the primary PLP transcript, is utilized in precursor mRNA (pre-mRNA) splicing.
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A catalogue of splice junction sequences.
  • S. Mount
  • Biology
    Nucleic acids research
  • 1982
The sequence CAAG/GTAGAGT was found to be a consensus of 139 exon-intron boundaries (or donor sequences) and (TC)nNCTAG/G was found of 130 intron-exon boundaries ( or acceptor sequences).
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Transcriptional control signals of a model eukaryotic protein-coding gene have been identified by a new procedure of in vitro mutagenesis. This method allows small clusters of nucleotide residues to
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Sequences which are essential for the initiation of specific transcription in vitro were shown to be located between 12 and 32 base pairs upstream from the 5' end of these genes.
The role of nucleotide sequences in splice site selection in eukaryotic pre-messenger RNA
It is shown that the archetypal consensus sequence is used efficiently, and the cryptic sites of β-globin are characterized: sequences alone can explain why these sites are not normally used.
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The studies indicate that transcriptional regulation of the somatostatin gene by cAMP requires protein kinase 2 activity and may depend upon a highly conserved promoter element.