Tissue-specific alternative splicing of the first exon generates two types of mRNAs in human aromatic L-amino acid decarboxylase.
Aromatic-L-amino-acid decarboxylase (AADC) is an enzyme that plays an essential role in synthesizing catecholamines and serotonin in neuronal and endocrine tissues. AADC has also been detected in other nonneuronal tissues including liver and kidney, although its physiological role in nonneuronal tissues has not yet been defined. Previously we have cloned a human AADC cDNA from a neuronal tissue (pheochromocytoma) [Ichinose, H., Kurosawa, Y., Titani, K., Fujita, K., & Nagatsu, T. (1989) Biochem. Biophys. Res. Commun. 164, 1024-1030] and the corresponding genomic DNA [Sumi-Ichinose, C., Ichinose, H., Takahashi, E., Hori, T., & Nagatsu, T. (1992) Biochemistry 31, 2229-2238]. Here we present isolation and characterization of AADC cDNA and genomic DNA from a nonneuronal tissue (human liver). The nonneuronal and neuronal AADC mRNAs differed only in the region corresponding to the untranslated first exon. The first exon for the nonneuronal-type mRNA was located 4.2 kilobases upstream to that for the neuronal-type mRNA and 22 kilobases from exon 2, to which it is spliced. Determination of the transcription initiation site indicated that the length of the nonneuronal-type exon 1 was 200 bp. A TATA box-like motif was located between positions -26 and -20 from the transcription initiation site. These results showed that an alternative usage of the first exon in the 5'-untranslated regions produces two types of mRNAs in AADC and suggested that alternative splicing would regulate the tissue-specific expression of AADC.
Ichinose
H
H
Institute for Comprehensive Medical Science, School of Medicine, Fujita Health University, Aichi, Japan.
Sumi-Ichinose
C
C
Ohye
T
T
Hagino
Y
Y
Fujita
K
K
Nagatsu
T
T
D000311:Adrenal Glands / Q000201:enzymology; D017398:Alternative Splicing; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000235:genetics*; D001483:Base Sequence; D002276:Carcinoid Tumor / Q000201:enzymology; D003001:Cloning, Molecular; D004247:DNA; D005091:Exons; D006801:Humans; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics*; D013378:Substantia Nigra / Q000201:enzymology; D014018:Tissue Distribution
D012333:RNA, Messenger; D004247:DNA; D001142:Aromatic-L-Amino-Acid Decarboxylases