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Article dans une revue

RNA-binding protein HuR enhances mineralocorticoid signaling in renal KC3AC1 cells under hypotonicity

Abstract : Mineralocorticoid receptor (MR) mediates the sodium-retaining action of aldosterone in the distal nephron. Herein, we decipher mechanisms by which hypotonicity increases MR expression in renal principal cells. We identify HuR (human antigen R), an mRNA-stabilizing protein, as an important posttranscriptional regulator of MR expression. Hypotonicity triggers a rapid and reversible nuclear export of HuR in renal KC3AC1 cells, as quantified by high-throughput microscopy. We also identify a key hairpin motif in the 3'-untranslated region of MR transcript, pivotal for the interaction with HuR and its stabilizing function. Next, we show that hypotonicity increases MR recruitment onto Sgk1 promoter, a well-known MR target gene, thereby enhancing aldosterone responsiveness. Our data shed new light on the crucial role of HuR as a stabilizing factor for the MR transcript and provide evidence for a short autoregulatory loop in which expression of a nuclear receptor transcriptionally regulating water and sodium balance is controlled by osmotic tone.
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https://hal.univ-grenoble-alpes.fr/hal-02459157
Contributeur : Nadia Cherradi <>
Soumis le : mercredi 29 janvier 2020 - 11:17:31
Dernière modification le : mercredi 16 septembre 2020 - 17:51:59

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Ingrid Lema, Larbi Amazit, Khadija Lamribet, Jérome Fagart, Anne Blanchard, et al.. RNA-binding protein HuR enhances mineralocorticoid signaling in renal KC3AC1 cells under hypotonicity. Cellular and Molecular Life Sciences, Springer Verlag, 2017, 74 (24), pp.4587-4597. ⟨10.1007/s00018-017-2594-x⟩. ⟨hal-02459157⟩

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