{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:20:40Z","timestamp":1791328840020,"version":"4.3.1"},"reference-count":46,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,7,6]],"date-time":"2017-07-06T00:00:00Z","timestamp":1499299200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,7,6]],"date-time":"2017-07-06T00:00:00Z","timestamp":1499299200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Aldosterone and the Mineralocorticoid Receptor (MR) control hydroelectrolytic homeostasis and alterations of mineralocorticoid signaling pathway are involved in the pathogenesis of numerous human diseases, justifying the need to decipher molecular events controlling MR expression level. Here, we show in renal cells that the RNA-Binding Protein, Human antigen R (HuR), plays a central role in the editing of MR transcript as revealed by a RNA interference strategy. We identify a novel \u03946 MR splice variant, which lacks the entire exon 6, following a HuR-dependent exon skipping event. Using isoform-specific TaqMan probes, we show that \u03946 MR variant is expressed in all MR-expressing tissues and cells and demonstrate that extracelullar tonicity regulates its renal expression. More importantly, this splice variant exerts dominant-negative effects on transcriptional activity of the full-length MR protein. Collectively, our data highlight a crucial role of HuR as a master posttranscriptional regulator of MR expression in response to osmotic stress. We demonstrate that hypotonicity, not only enhances MR mRNA stability, but also decreases expression of the \u03946 MR variant, thus potentiating renal MR signaling. These findings provide compelling evidence for an autoregulatory feedback loop for the control of sodium homeostasis through posttranscriptional events, likely relevant in renal pathophysiological situations.<\/jats:p>","DOI":"10.1038\/s41598-017-04838-8","type":"journal-article","created":{"date-parts":[[2017,6,30]],"date-time":"2017-06-30T15:28:44Z","timestamp":1498836524000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["HuR-Dependent Editing of a New Mineralocorticoid Receptor Splice Variant Reveals an Osmoregulatory Loop for Sodium Homeostasis"],"prefix":"10.1038","volume":"7","author":[{"given":"Ingrid","family":"Lema","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larbi","family":"Amazit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khadija","family":"Lamribet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Fagart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Blanchard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Lomb\u00e8s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Cherradi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Say","family":"Viengchareun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,7,6]]},"reference":[{"key":"4838_CR1","doi-asserted-by":"crossref","first-page":"e012","DOI":"10.1621\/nrs.05012","volume":"5","author":"S Viengchareun","year":"2007","unstructured":"Viengchareun, S. et al. The mineralocorticoid receptor: insights into its molecular and (patho)physiological biology. Nucl. Recept. Signal \n                           5, e012 (2007).","journal-title":"Nucl. Recept. Signal"},{"key":"4838_CR2","doi-asserted-by":"publisher","first-page":"9424","DOI":"10.1073\/pnas.95.16.9424","volume":"95","author":"S Berger","year":"1998","unstructured":"Berger, S. et al. Mineralocorticoid receptor knockout mice: pathophysiology of Na+ metabolism. Proc. Natl. Acad. Sci. USA \n                           95, 9424\u20139429 (1998).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"4838_CR3","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1038\/966","volume":"19","author":"DS Geller","year":"1998","unstructured":"Geller, D. S. et al. Mutations in the mineralocorticoid receptor gene cause autosomal dominant pseudohypoaldosteronism type I. Nat. Genet. \n                           19, 279\u2013281 (1998).","journal-title":"Nat. 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Role of post-transcriptional regulation of mRNA stability in renal pathophysiology: focus on chronic kidney disease. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. \n                           31, 457\u2013468 (2017).","journal-title":"FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol."},{"key":"4838_CR7","doi-asserted-by":"publisher","first-page":"2213","DOI":"10.1681\/ASN.2013091023","volume":"25","author":"S Viengchareun","year":"2014","unstructured":"Viengchareun, S. et al. Hypertonicity compromises renal mineralocorticoid receptor signaling through Tis11b-mediated post-transcriptional control. J. Am. Soc. Nephrol. JASN \n                           25, 2213\u20132221 (2014).","journal-title":"J. Am. Soc. Nephrol. JASN"},{"key":"4838_CR8","doi-asserted-by":"publisher","first-page":"3168","DOI":"10.1007\/s00018-008-8252-6","volume":"65","author":"MN Hinman","year":"2008","unstructured":"Hinman, M. N. & Lou, H. Diverse molecular functions of Hu proteins. Cell. Mol. Life Sci. 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