Single nucleotide polymorphism rs13079080 is associated with differential regulation of the succinate receptor 1 (SUCNR1) gene by miRNA-4470
| Autor: | Anneke I. den Hollander, Elja Louer, Peter M.T. Deen, Ana Mãdãlina Ion, Laura Lorés-Motta |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
retina Genotype Metabolite Single-nucleotide polymorphism Biology AMD medicine.disease_cause Polymorphism Single Nucleotide Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12] Receptors G-Protein-Coupled 03 medical and health sciences chemistry.chemical_compound Macular Degeneration 0302 clinical medicine microRNA Gene expression Succinate receptor 1 medicine Humans Molecular Biology Gene 3' Untranslated Regions Genetic Association Studies 030304 developmental biology Aged Aged 80 and over 0303 health sciences micro-RNA Differential regulation Cell Biology Cell biology MicroRNAs Oxidative Stress Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11] chemistry SUCNR1 030220 oncology & carcinogenesis Case-Control Studies gene expression Female Oxidative stress Research Paper |
| Zdroj: | RNA Biology, 16, 11, pp. 1547-1554 RNA Biology RNA Biology, 16, 1547-1554 |
| ISSN: | 1547-6286 |
| Popis: | Contains fulltext : 208567.pdf (Publisher’s version ) (Open Access) Oxidative stress is a feature of many common diseases. It leads to excessive formation and subsequent release of the mitochondrial metabolite succinate, which acts as a signalling molecule through binding the succinate receptor (SUCNR1). Recently, a potential role for SUCNR1 was proposed in age-related macular degeneration (AMD), a common cause of vision loss in the elderly associated with increased oxidative stress. Here, we evaluated the potential effect of genetic variants in SUCNR1 on its expression through differential micro-RNA (miRNA) binding to target mRNA, and investigated the relevance of altered SUCNR1 expression in AMD pathogenesis. We analysed common SUCNR1 SNPs for potential miRNA binding sites and identified rs13079080, located in the 3'-UTR and binding site for miRNA-4470. Both miRNA-4470 and SUCNR1 were found to be expressed in human retina. Moreover, using a luciferase reporter assay, a 60% decrease in activity was observed when miRNA-4470 was co-expressed with the C allele compared to the T allele of rs13079080. Finally, genotyping rs13079080 in an AMD case-control cohort revealed a protective effect of the TT genotype on AMD compared to the CC genotype (p = 0.007, odds ratio = 0.66). However, the association was not confirmed in the case-control study of the International AMD Genomics Consortium. Our study demonstrates that the T allele of rs13079080 in SUCNR1 disrupts a binding site for miRNA-4470, potentially increasing SUCNR1 expression and consequently increasing the capacity of sensing and dealing with oxidative stress. Therefore, it would be worthwhile assessing the relevance of rs13079080 in other oxidative stress-associated diseases in future studies. 01 november 2019 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|