RNA-binding protein HuR enhances mineralocorticoid signaling in renal KC3AC1 cells under hypotonicity
Ingrid J. Lema
(1)
,
Larbi Amazit
(1)
,
Khadija Lamribet
(2)
,
Jérome Fagart
(1)
,
Anne Blanchard
(3)
,
Marc Lombès
(4)
,
Nadia Cherradi
(5)
,
Say Viengchareun
(4)
1
Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique
2 Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique
3 UPD5 Médecine - Université Paris Descartes - Faculté de Médecine
4 UP11 - Université Paris-Sud - Paris 11
5 LAPV - Angiogenèse hormono-regulée et angiogenèse tumorale
2 Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique
3 UPD5 Médecine - Université Paris Descartes - Faculté de Médecine
4 UP11 - Université Paris-Sud - Paris 11
5 LAPV - Angiogenèse hormono-regulée et angiogenèse tumorale
Ingrid J. Lema
- Fonction : Auteur
- PersonId : 951596
Larbi Amazit
- Fonction : Auteur
- PersonId : 880367
Khadija Lamribet
- Fonction : Auteur
- PersonId : 740020
- IdHAL : khadija-lamribet
- IdRef : 253130484
Jérome Fagart
- Fonction : Auteur
- PersonId : 966820
Anne Blanchard
- Fonction : Auteur
- PersonId : 759639
- ORCID : 0000-0002-0815-0586
Nadia Cherradi
- Fonction : Auteur
- PersonId : 180012
- IdHAL : nadia-cherradi
- ORCID : 0000-0002-4292-774X
- IdRef : 185869831
Say Viengchareun
- Fonction : Auteur
- PersonId : 748888
- IdHAL : say-viengchareun
- ORCID : 0000-0003-4280-3250
- IdRef : 097146846
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.
Domaines
Sciences de l'Homme et SociétéFormat du dépôt | Notice |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
RNA-binding protein HuR enhances mineralocorticoid signaling in renal KC3AC1 cells under hypotonicity
|
Résumé |
en
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.
|
Auteur(s) |
Ingrid J. Lema
1
, Larbi Amazit
1
, Khadija Lamribet
2
, Jérome Fagart
1
, Anne Blanchard
3
, Marc Lombès
4
, Nadia Cherradi
5
, Say Viengchareun
4
1
Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique
( 3051 )
- Faculté de médecine 63, Rue Gabriel Peri 94276 LE KREMLIN BICETRE
- France
2
Signalisation Hormonale, Physiopathologie Endocrinienne et Métabolique
( 424755 )
- Faculté de Médecine Paris Sud - 63 rue Gabriel Péri 94276 Le Kremlin Bicêtre Cedex
- France
3
UPD5 Médecine -
Université Paris Descartes - Faculté de Médecine
( 12951 )
- 15 rue de l'École de médecine - 75270 Paris Cedex 06
- France
4
UP11 -
Université Paris-Sud - Paris 11
( 92966 )
- Bâtiment 300 - 91405 Orsay cedex
- France
5
LAPV -
Angiogenèse hormono-regulée et angiogenèse tumorale
( 40553 )
- France
|
Langue du document |
Anglais
|
Nom de la revue |
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Audience |
Internationale
|
Date de publication |
2017-12
|
Volume |
74
|
Numéro |
24
|
Page/Identifiant |
4587-4597
|
Domaine(s) |
|
Mots-clés |
en
Aldosterone, Mineralocorticoid receptor, Nucleocytoplasmic trafficking, Osmotic stress, Posttranscriptional regulation, Sodium transport
|
DOI | 10.1007/s00018-017-2594-x |
Pubmed Id | 28744670 |
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