RNA-binding protein HuR enhances mineralocorticoid signaling in renal KC3AC1 cells under hypotonicity - Université Grenoble Alpes
Article Dans Une Revue Cellular and Molecular Life Sciences Année : 2017

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

Résumé

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.

Dates et versions

hal-02459157 , version 1 (29-01-2020)

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Citer

Ingrid J. 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, 2017, 74 (24), pp.4587-4597. ⟨10.1007/s00018-017-2594-x⟩. ⟨hal-02459157⟩
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