Post-Transcriptional Regulation of Renalase Gene by miR-29 and miR-146 MicroRNAs: Implications for Cardiometabolic Disorders. Issue 16 (14th August 2015)

• Record Type: Journal Article
• Authors: Kalyani, Ananthamohan; Sonawane, Parshuram J.; Khan, Abrar Ali; Subramanian, Lakshmi; Ehret, Georg B.; Mullasari, Ajit S.; Mahapatra, Nitish R.
• Is Part Of: Journal of molecular biology. Volume 427:Issue 16(2015:Aug. 15)
• Page Start: 2629
• Page End: 2646
• Publication Date: 2015-08-14
• Subjects: BPH blood pressure high -- BPL blood pressure low -- BPN blood pressure normal -- DBP diastolic blood pressure -- GWAS genome-wide association studies -- miRNA microRNA -- SBP systolic blood pressure -- SNP single nucleotide polymorphism; renalase -- microRNA -- post-transcriptional -- single nucleotide polymorphism -- cardiometabolic traits; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2015.07.003
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: 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 ( u n t ranslated r egion) 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. Graphical abstract: Highlights: Renalase is a novel regulator of cardiovascular/metabolic/renal diseases. MicroRNAs belonging to miR-29 and miR-146 families interact with mouse and human renalase mRNA. Renalase and miR-29b expressions show an inverse correlation in genetically hypertensive mice. A common genetic variation in human renalase (rs10749571) creates a miR-146a binding site. The rs10749571 genetic variation may influence blood pressure/glucose/triglyceride levels.