1. Human peroxiredoxin 5 gene organization, initial characterization of its promoter and identification of alternative forms of mRNA
- Author
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Valérie Van der Eecken, André Clippe, Jehanne Berck, Elee Duconseille, Alfred Bernard, C Boone, Bernard Knoops, Ingrid Banmeyer, Nhu Tiên Nguyên-nhu, and H. Cherif
- Subjects
5' Flanking Region ,5' flanking region ,Molecular Sequence Data ,Biophysics ,Biology ,Biochemistry ,Exon ,Structural Biology ,Genetics ,Humans ,Amino Acid Sequence ,Promoter Regions, Genetic ,Transcription factor ,Gene ,Genomic organization ,Base Sequence ,Alternative splicing ,Intron ,Exons ,Peroxiredoxins ,Introns ,Alternative Splicing ,Peroxidases ,Transcription Initiation Site ,Peroxiredoxin - Abstract
Peroxiredoxin 5 (PRDX5) is a mammalian thioredoxin peroxidase ubiquitously expressed in tissues. Its role as antioxidant enzyme has been previously supported in different pathological situations. In this study, we determined the complete human PRDX5 genomic organization and isolated the 5'-flanking region of the gene. Human PRDX5 gene is composed of six exons and five introns similarly to other chordate PRDX5 genes. Several single nucleotide polymorphisms were identified. Six out of them have amino acid substitutions in protein-coding region. Analysis of the 5'-flanking region of human PRDX5 revealed the presence of a TATA-less promoter containing a canonical CpG island and several putative response elements for transcription factors. To analyze the regulatory mechanisms controlling human PRDX5 expression, we characterized the 5'-flanking region by cloning various segments of this region in front of a luciferase reporter sequence. Transfection in HepG2 cells indicate that the 5'-flanking region contains regulatory elements for constitutive expression of human PRDX5. Multiple transcription start sites were also identified by 5'-RACE-PCR in human liver. Moreover, although no corresponding proteins were reported, we present new alternative splicing variants encoded specifically by human PRDX5 gene. The characterization of human PRDX5 gene revealed the complexity of its regulation and a high variability of sequences that might be associated with pathological situations.
- Published
- 2006