MicroRNAs miR-124 and miR-135a are potential regulators of the mineralocorticoid receptor gene (NR3C2) expression.
MicroRNAs (miRNAs) comprise a post-transcriptional layer of gene regulation shown to be involved in diverse physiological processes. We aimed to study whether regulatory networks that determine susceptibility to hypertension may involve a miRNA component. Screening of loci, involved in renal water-salt balance regulation, highlighted the mineralocorticoid receptor gene NR3C2 as a potential target for several miRNAs. A luciferase assay demonstrated that miR-124 and miR-135a suppress NR3C2 3'UTR reporter construct activity 1.5- and 2.2-fold, respectively. As the tested miRNAs did not reduce the levels of target mRNA, we suggest that the binding of miR-124 and miR-135a to NR3C2 3'UTR contributes to the translational, not transcriptional regulation of the gene. Co-expression of two different miRNAs did not increase the repression of the reporter gene, indicating no additive or synergistic effects between the tested miRNAs. Our results demonstrate that by repressing the mineralocorticoid receptor gene NR3C2, miR-124 and miR-135a could participate in the regulation of renin-angiotensin-aldosterone system and thereby might be involved in blood pressure regulation.
Sõber
Siim
S
Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, Estonia. siims@ut.ee
Laan
Maris
M
Annilo
Tarmo
T
D001794:Blood Pressure / Q000235:genetics; D019295:Computational Biology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics; D035683:MicroRNAs / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D018161:Receptors, Mineralocorticoid / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000235:genetics*; D014158:Transcription, Genetic
C509207:MIRN124 microRNA, human; C544965:MIRN135 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D008156:Luciferases