Post-Transcriptional Regulation of Renalase Gene by miR-29 and miR-146 MicroRNAs: Implications for Cardiometabolic Disorders

Autor: Ananthamohan Kalyani, Parshuram J. Sonawane, Nitish R. Mahapatra, Lakshmi Subramanian, Ajit S. Mullasari, Georg Ehret, Abrar A. Khan
Rok vydání: 2015
Předmět:
genetic association
MicroRNAs/biosynthesis/genetics
Blood Pressure
Genome-wide association study
animal cell
genetic analysis
Binding Sites/genetics
kidney parenchyma
Mice
cardiovascular disease
genetics
RNA transcription
microRNA 146
ddc:616
Mirn146 microRNA
mouse
microRNA
Mus
priority journal
3' Untranslated Regions/genetics
Cardiovascular Diseases
neuroblastoma cell
transient transfection
transcription regulation
renalase
down regulation
medicine.medical_specialty
Hypotension/enzymology/genetics
Single-nucleotide polymorphism
animal tissue
mathematical genetics
MIRN29 microRNA
human
Humans
cardiometabolic disorder
RNA folding
human
normal human
Hypertension/enzymology/genetics
protein expression
Molecular Biology
mouse
microRNA 29c
MIRN146 microRNA
human
binding site
Monoamine Oxidase/biosynthesis/genetics
animal model
human cell
microRNA 146a
microRNA 29a
microRNA 146b
microRNA 29b
diastolic blood pressure
amine oxidase (flavin containing)
3' untranslated region
triacylglycerol blood level
glucose blood level
Endocrinology
biosynthesis
upregulation
metabolic disorder
Untranslated region
genomic DNA
single nucleotide polymorphism
Structural Biology
cardiometabolic risk
animal
glucose
oxidoreductase
3' Untranslated Regions
Renalase
Genetics
messenger RNA
Blood Pressure/genetics/physiology
unclassified drug
enzyme activity
HEK293 cell line
Hypertension
enzyme regulation
triacylglycerol
Hypotension
microRNA 29
enzymology
Biology
Gene Expression Regulation/genetics
Polymorphism
Single Nucleotide
Cell Line
Tumor
Internal medicine
Cardiovascular Diseases/genetics
medicine
Animals
controlled study
Allele
Monoamine Oxidase
Gene
Post-transcriptional regulation
cell culture
nonhuman
Binding Sites
MIRN29 microRNA
mouse
essential hypertension
tumor cell line
prediction
RNA binding
MicroRNAs
HEK293 Cells
Gene Expression Regulation
physiology
gene expression
Genome-Wide Association Study
Zdroj: Journal of Molecular Biology, Vol. 427, No 16 (2015) pp. 2629-2646
ISSN: 0022-2836
Popis: Renalase, a recently identified oxidoreductase, is emerging as a novel regulator of cardiovascular and metabolic disease states. The mechanism of regulation of renalase gene, especially at the post-transcriptional level, is completely unknown. We set out to investigate the possible role of microRNAs in regulation of renalase gene in this study. Computational predictions using multiple algorithms coupled with systematic functional analysis revealed specific interactions of miR-29a/b/c and miR-146a/b with mouse and human renalase 3?-UTR (untranslated region) in cultured cells. Next, we estimated miR-29b and miR-146a, as well as renalase expression, in genetically hypertensive blood pressure high and genetically hypotensive blood pressure low mice. Kidney tissues from blood pressure high mice showed diminished (? 1.6- to 1.8-fold) renalase mRNA/protein levels and elevated (? 2.2-fold) miR-29b levels as compared to blood pressure low mice. A common single nucleotide polymorphism in human renalase 3?-UTR (C/T
rs10749571) creates a binding site for miR-146a
consistently, miR-146a down-regulated human renalase 3?-UTR/luciferase activity in case of the T allele suggesting its potential role in regulation of renalase in humans. Indeed, genome-wide association studies revealed directionally concordant association of rs10749571 with diastolic blood pressure, glucose and triglyceride levels in large human populations (n ? 58,000-96,000 subjects). This study provides evidence for post-transcriptional regulation of renalase gene by miR-29 and miR-146 and has implications for inter-individual variations on cardiometabolic traits. � 2015 Elsevier Ltd. All rights reserved.
Databáze: OpenAIRE
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