Human peroxiredoxin 5 gene organization, initial characterization of its promoter and identification of alternative forms of mRNA.
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.
Nguyên-Nhu
Nhu Tiên
NT
Laboratory of Cell Biology, ISV, Department of Biology, Université catholique de Louvain, Place Croix du Sud 5, B-1348 Louvain-la-Neuve, Belgium.
Berck
Jehanne
J
Clippe
André
A
Duconseille
Elee
E
Cherif
Hanane
H
Boone
Christophe
C
Van der Eecken
Valérie
V
Bernard
Alfred
A
Banmeyer
Ingrid
I
Knoops
Bernard
B
D024506:5' Flanking Region / Q000235:genetics; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D005091:Exons; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D010544:Peroxidases / Q000235:genetics*; D054464:Peroxiredoxins; D011401:Promoter Regions, Genetic; D024363:Transcription Initiation Site
D010544:Peroxidases; C515974:PRDX5 protein, human; D054464:Peroxiredoxins