PMID- 31926050
OWN - NLM
STAT- MEDLINE
DCOM- 20210603
LR  - 20210603
IS  - 1755-148X (Electronic)
IS  - 1755-1471 (Linking)
VI  - 33
IP  - 4
DP  - 2020 Jul
TI  - Pathogenesis of a variant in the 5' untranslated region of ADAR1 in 
      dyschromatosis symmetrica hereditaria.
PG  - 591-600
LID - 10.1111/pcmr.12863 [doi]
AB  - Dyschromatosis symmetrica hereditaria (DSH) is a pigmentary genodermatosis caused 
      by mutations in ADAR1. In this study, we performed mutation analysis on a family 
      that included typical DSH patients. No mutations were found in any coding regions 
      or exon-intron boundary regions of ADAR1, but a previously unreported non-coding 
      heterozygous variant, c.-60A>G, was found in the 5' untranslated region (5'UTR) 
      of ADAR1 in the proband and her mother. The function of 5'UTR in mRNA is not 
      well-understood. To understand the pathogenesis of the variant and the function 
      of the 5'UTR of ADAR1, we constructed two reporter genes carrying the ADAR1 5'UTR 
      sequence with/without the variant between the PGK promoter and a luciferase 
      coding sequence, and performed luciferase assays, semi-quantitative PCR analyses, 
      and polysomal assays. In human melanocytes, c.-60A>G induced a 16% reduction in 
      transcription and a 51% reduction in translation. Our results indicate that the 
      5'UTR c.-60A>G variant adversely affects the post-transcriptional step in gene 
      expression, leading to DSH. Detailed functional assays of the 5'UTR of ADAR1 in 
      the present study revealed the gene expression to be not only downregulated, but 
      also upregulated by defects in 5'UTR depending on the locations. The regulation 
      of translation by 5'UTR is very complicated.
CI  - (c) 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Suganuma, Mutsumi
AU  - Suganuma M
AD  - Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, 
      Japan.
FAU - Kono, Michihiro
AU  - Kono M
AUID- ORCID: 0000-0003-2639-1583
AD  - Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, 
      Japan.
FAU - Yamanaka, Masayoshi
AU  - Yamanaka M
AD  - Division of Dermatology, Ishii Hospital, Isezaki, Japan.
FAU - Akiyama, Masashi
AU  - Akiyama M
AD  - Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, 
      Japan.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200127
PL  - England
TA  - Pigment Cell Melanoma Res
JT  - Pigment cell & melanoma research
JID - 101318927
RN  - 0 (5' Untranslated Regions)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA-Binding Proteins)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 3.5.4.37 (ADAR protein, human)
RN  - EC 3.5.4.4 (Adenosine Deaminase)
RN  - Dyschromatosis symmetrica hereditaria 1
SB  - IM
MH  - 5' Untranslated Regions/*genetics
MH  - Adenosine Deaminase/*genetics
MH  - Base Sequence
MH  - Cell Line, Tumor
MH  - Computer Simulation
MH  - DNA Mutational Analysis
MH  - Female
MH  - Gene Expression Regulation
MH  - Genes, Reporter
MH  - *Genetic Variation
MH  - Heterozygote
MH  - Humans
MH  - Luciferases/metabolism
MH  - Nucleic Acid Conformation
MH  - Pigmentation Disorders/*congenital/genetics
MH  - Polyribosomes/metabolism
MH  - Protein Biosynthesis
MH  - RNA, Messenger/genetics/metabolism
MH  - RNA-Binding Proteins/*genetics
MH  - Transcription, Genetic
MH  - Young Adult
OTO - NOTNLM
OT  - 5' untranslated region
OT  - adenosine deaminases acting on RNA1
OT  - dyschromatosis symmetrica hereditaria
OT  - polysomal profiling
OT  - translation
EDAT- 2020/01/12 06:00
MHDA- 2021/06/04 06:00
CRDT- 2020/01/12 06:00
PHST- 2019/08/01 00:00 [received]
PHST- 2019/10/30 00:00 [revised]
PHST- 2020/01/08 00:00 [accepted]
PHST- 2020/01/12 06:00 [pubmed]
PHST- 2021/06/04 06:00 [medline]
PHST- 2020/01/12 06:00 [entrez]
AID - 10.1111/pcmr.12863 [doi]
PST - ppublish
SO  - Pigment Cell Melanoma Res. 2020 Jul;33(4):591-600. doi: 10.1111/pcmr.12863. Epub 
      2020 Jan 27.