The assessment of noncoding variant of PPOX gene in variegate porphyria reveals post-transcriptional role of the 5′ untranslated exon 1

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The PPOX gene encodes for the protoporphyrinogen oxidase, which is involved in heme production. The partial deficiency of protoporphyrinogen oxidase causes variegate porphyria. The tissue-specific regulation of other heme biosynthetic enzymes is extensively studied, but the information concerning transcriptional and post-transcriptional regulation of PPOX gene expression is scarcely available. In this study, we characterized functions of three variants identified in the regulatory regions of the PPOX gene, which show a novel role for the 5′ untranslated exon 1. Using luciferase assays and RNA analysis, we demonstrated that only c.1-883G > C promoter variant causes a significant loss in the transcriptional activity of PPOX gene whereas c.1-413G > T 5′ UTR variant inhibits translation of PPOX mRNA and c.1-176G > A splicing variant causes 4 bp deletion in 5′ UTR of PPOX mRNA variant 2. These observations indicate that the regulation of PPOX gene expression can also occur through a post-transcriptional modulation of the amount of gene product and that this modulation can be mediated by 5′ untranslated exon 1. Moreover this study confirms that these regulatory regions represent an important molecular target for the pathogenesis of variegate porphyria.

Original languageEnglish
Pages (from-to)48-53
Number of pages6
JournalBlood Cells, Molecules, and Diseases
Volume61
DOIs
Publication statusPublished - Oct 1 2016

Fingerprint

Variegate Porphyria
Exons
Nucleic Acid Regulatory Sequences
5' Untranslated Regions
Gene Expression Regulation
Heme
Genes
Protoporphyrinogen Oxidase
Protein Biosynthesis
Luciferases
RNA
Messenger RNA
Enzymes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Hematology
  • Cell Biology

Cite this

@article{9f8900d0ea554a01aa5f3b7d7645e90a,
title = "The assessment of noncoding variant of PPOX gene in variegate porphyria reveals post-transcriptional role of the 5′ untranslated exon 1",
abstract = "The PPOX gene encodes for the protoporphyrinogen oxidase, which is involved in heme production. The partial deficiency of protoporphyrinogen oxidase causes variegate porphyria. The tissue-specific regulation of other heme biosynthetic enzymes is extensively studied, but the information concerning transcriptional and post-transcriptional regulation of PPOX gene expression is scarcely available. In this study, we characterized functions of three variants identified in the regulatory regions of the PPOX gene, which show a novel role for the 5′ untranslated exon 1. Using luciferase assays and RNA analysis, we demonstrated that only c.1-883G > C promoter variant causes a significant loss in the transcriptional activity of PPOX gene whereas c.1-413G > T 5′ UTR variant inhibits translation of PPOX mRNA and c.1-176G > A splicing variant causes 4 bp deletion in 5′ UTR of PPOX mRNA variant 2. These observations indicate that the regulation of PPOX gene expression can also occur through a post-transcriptional modulation of the amount of gene product and that this modulation can be mediated by 5′ untranslated exon 1. Moreover this study confirms that these regulatory regions represent an important molecular target for the pathogenesis of variegate porphyria.",
author = "Valeria Fiorentino and Valentina Brancaleoni and Francesca Granata and Giovanna Graziadei and {Di Pierro}, Elena",
year = "2016",
month = "10",
day = "1",
doi = "10.1016/j.bcmd.2016.08.002",
language = "English",
volume = "61",
pages = "48--53",
journal = "Blood Cells, Molecules, and Diseases",
issn = "1079-9796",
publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - The assessment of noncoding variant of PPOX gene in variegate porphyria reveals post-transcriptional role of the 5′ untranslated exon 1

AU - Fiorentino, Valeria

AU - Brancaleoni, Valentina

AU - Granata, Francesca

AU - Graziadei, Giovanna

AU - Di Pierro, Elena

PY - 2016/10/1

Y1 - 2016/10/1

N2 - The PPOX gene encodes for the protoporphyrinogen oxidase, which is involved in heme production. The partial deficiency of protoporphyrinogen oxidase causes variegate porphyria. The tissue-specific regulation of other heme biosynthetic enzymes is extensively studied, but the information concerning transcriptional and post-transcriptional regulation of PPOX gene expression is scarcely available. In this study, we characterized functions of three variants identified in the regulatory regions of the PPOX gene, which show a novel role for the 5′ untranslated exon 1. Using luciferase assays and RNA analysis, we demonstrated that only c.1-883G > C promoter variant causes a significant loss in the transcriptional activity of PPOX gene whereas c.1-413G > T 5′ UTR variant inhibits translation of PPOX mRNA and c.1-176G > A splicing variant causes 4 bp deletion in 5′ UTR of PPOX mRNA variant 2. These observations indicate that the regulation of PPOX gene expression can also occur through a post-transcriptional modulation of the amount of gene product and that this modulation can be mediated by 5′ untranslated exon 1. Moreover this study confirms that these regulatory regions represent an important molecular target for the pathogenesis of variegate porphyria.

AB - The PPOX gene encodes for the protoporphyrinogen oxidase, which is involved in heme production. The partial deficiency of protoporphyrinogen oxidase causes variegate porphyria. The tissue-specific regulation of other heme biosynthetic enzymes is extensively studied, but the information concerning transcriptional and post-transcriptional regulation of PPOX gene expression is scarcely available. In this study, we characterized functions of three variants identified in the regulatory regions of the PPOX gene, which show a novel role for the 5′ untranslated exon 1. Using luciferase assays and RNA analysis, we demonstrated that only c.1-883G > C promoter variant causes a significant loss in the transcriptional activity of PPOX gene whereas c.1-413G > T 5′ UTR variant inhibits translation of PPOX mRNA and c.1-176G > A splicing variant causes 4 bp deletion in 5′ UTR of PPOX mRNA variant 2. These observations indicate that the regulation of PPOX gene expression can also occur through a post-transcriptional modulation of the amount of gene product and that this modulation can be mediated by 5′ untranslated exon 1. Moreover this study confirms that these regulatory regions represent an important molecular target for the pathogenesis of variegate porphyria.

UR - http://www.scopus.com/inward/record.url?scp=84983550749&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84983550749&partnerID=8YFLogxK

U2 - 10.1016/j.bcmd.2016.08.002

DO - 10.1016/j.bcmd.2016.08.002

M3 - Article

AN - SCOPUS:84983550749

VL - 61

SP - 48

EP - 53

JO - Blood Cells, Molecules, and Diseases

JF - Blood Cells, Molecules, and Diseases

SN - 1079-9796

ER -