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RNA-binding protein HuR enhances mineralocorticoid signaling in renal KC3AC1 cells under hypotonicity.
- Source :
-
Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2017 Dec; Vol. 74 (24), pp. 4587-4597. Date of Electronic Publication: 2017 Jul 25. - Publication Year :
- 2017
-
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.
- Subjects :
- 3' Untranslated Regions genetics
Active Transport, Cell Nucleus genetics
Aldosterone metabolism
Gene Expression Regulation genetics
HEK293 Cells
Humans
Immediate-Early Proteins metabolism
Kidney physiology
Osmosis physiology
Promoter Regions, Genetic genetics
Protein Serine-Threonine Kinases metabolism
RNA Processing, Post-Transcriptional genetics
RNA, Messenger metabolism
Transcription, Genetic genetics
ELAV-Like Protein 1 metabolism
Kidney metabolism
Mineralocorticoids metabolism
Osmotic Pressure physiology
RNA-Binding Proteins metabolism
Receptors, Mineralocorticoid metabolism
Signal Transduction physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1420-9071
- Volume :
- 74
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Cellular and molecular life sciences : CMLS
- Publication Type :
- Academic Journal
- Accession number :
- 28744670
- Full Text :
- https://doi.org/10.1007/s00018-017-2594-x