Genomic organization of human arylamine N-acetyltransferase Type I reveals alternative promoters that generate different 5'-UTR splice variants with altered translational activities

Butcher, N. J., Arulpragasam, A., Goh, H. L., Davey, Tamara and Minchin, Rodney F. (2005) Genomic organization of human arylamine N-acetyltransferase Type I reveals alternative promoters that generate different 5'-UTR splice variants with altered translational activities. Biochemical Journal, 387 1: 119-127. doi:10.1042/BJ20040903


Author Butcher, N. J.
Arulpragasam, A.
Goh, H. L.
Davey, Tamara
Minchin, Rodney F.
Title Genomic organization of human arylamine N-acetyltransferase Type I reveals alternative promoters that generate different 5'-UTR splice variants with altered translational activities
Journal name Biochemical Journal   Check publisher's open access policy
ISSN 0264-6021
Publication date 2005-04
Sub-type Article (original research)
DOI 10.1042/BJ20040903
Volume 387
Issue 1
Start page 119
End page 127
Total pages 9
Place of publication London, England, U.K.
Publisher Portland Press Ltd
Collection year 2005
Language eng
Subject C1
111501 Basic Pharmacology
1115 Pharmacology and Pharmaceutical Sciences
0601 Biochemistry and Cell Biology
Abstract In humans, a polymorphic gene encodes the drug-metabolizing enzyme NATI (arylamine N-acetyltransferase Type 1), which is widely expressed throughout the body. While the protein-coding region of NATI is contained within a single exon, examination of the human EST (expressed sequence tag) database at the NCBI revealed the presence of nine separate exons, eight of which were located in the 5'non-coding region of NATI. Differential splicing produced at least eight unique mRNA isoforms that could be grouped according to the location of the first exon, which suggested that NATI expression occurs from three alternative promoters. Using RT (reverse transcriptase)-PCR, we identified one major transcript in various epithelial cells derived from different tissues. In contrast, multiple transcripts were observed in blood-derived cell lines (CEM, THP-1 and Jurkat), with a novel variant, not identified in the EST database, found in CEM cells only. The major splice variant increased gene expression 9-11-fold in a luciferase reporter assay, while the other isoforrns were similar or slightly greater than the control. We examined the upstream region of the most active splice variant in a promoter-reporter assay, and isolated a 257 bp sequence that produced maximal promoter activity. This sequence lacked a TATA box, but contained a consensus Sp1 site and a CAAT box, as well as several other putative transcription-factor-binding sites. Cell-specific expression of the different NATI transcripts may contribute to the variation in NATI activity in vivo.
Keyword N-acetyltransferase
arylamine N-transferase (NAT)
promoter
splice variant
translation
5' untranslated region (5'-UTR)
N-acetyltransferase-1 Nat1
Nucleotide-sequence
Secondary Structure
Escherichia-coli
Human Liver
Identification
Inactivation
Acetylation
Expression
Cancer
Biochemistry & Molecular Biology
Q-Index Code C1
Additional Notes DOI 10.1042/BJ20040903

 
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Created: Wed, 15 Aug 2007, 06:17:38 EST