title: Regulation of WNK1 expression by miR-192 and aldosterone.
abstract: WNK1 and WNK4 encode two members of the WNK serine-threonine kinase subfamily. Greater WNK1 expression associates with higher BP. A combination of promoters, enhancers, repressors, and insulators regulate WNK1 expression, but whether microRNAs also modulate WNK1 expression is unknown. Here, computational analysis revealed the presence of a target sequence for miR-192 and miR-215 at the same site in the 3' untranslated region of the ubiquitous L- and the kidney-specific KS-WNK1. We functionally validated this target sequence by transient transfection and reporter assays. Although we observed expression of both miRs along the distal nephron, only miR-192 regulated endogenous WNK1 ex vivo. Furthermore, a potassium load, sodium depletion, and aldosterone infusion each significantly reduced miR-192 expression in the kidney. Taken together, these results suggest a miR-driven mechanism of gene regulation by aldosterone and a role for miR-192 in the regulation of sodium and potassium balance in the kidney.
authors.affiliation: INSERM U970, Paris Centre for Cardiovascular Research, Paris, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Elvira-Matelot
authors.forename: Xiao-ou
authors.initials: XO
authors.lastname: Zhou
authors.forename: Nicolette
authors.initials: N
authors.lastname: Farman
authors.forename: Geneviève
authors.initials: G
authors.lastname: Beaurain
authors.forename: Alexandra
authors.initials: A
authors.lastname: Henrion-Caude
authors.forename: Juliette
authors.initials: J
authors.lastname: Hadchouel
authors.forename: Xavier
authors.initials: X
authors.lastname: Jeunemaitre
mesh_terms: D020413:3' Untranslated Regions; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004285:Dogs; D007686:Kidney Tubules, Distal / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D015778:Minor Histocompatibility Antigens; D011188:Potassium / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012982:Sodium, Dietary / Q000378:metabolism; D000076204:WNK Lysine-Deficient Protein Kinase 1
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D015778:Minor Histocompatibility Antigens; C539618:Mirn192 microRNA, mouse; D012982:Sodium, Dietary; D000450:Aldosterone; D017346:Protein Serine-Threonine Kinases; D000076204:WNK Lysine-Deficient Protein Kinase 1; C498744:Wnk1 protein, mouse; D011188:Potassium
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