RNA binding protein Caprin-2 is a pivotal regulator of the central osmotic defense response
In response to an osmotic challenge, the synthesis of the antidiuretic hormone arginine vasopressin (AVP) increases in the hypothalamus, and this is accompanied by extension of the 3′ poly(A) tail of the AVP mRNA, and the up-regulation of the expression of RNA binding protein Caprin-2. Here we show...
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doaj-2850447c01b0476aa8395b5192ac74442021-05-05T00:06:25ZengeLife Sciences Publications LtdeLife2050-084X2015-11-01410.7554/eLife.09656RNA binding protein Caprin-2 is a pivotal regulator of the central osmotic defense responseAgnieszka Konopacka0Mingkwan Greenwood1Su-Yi Loh2Julian Paton3David Murphy4School of Clinical Sciences, University of Bristol, Bristol, United KingdomSchool of Clinical Sciences, University of Bristol, Bristol, United KingdomDepartment of Physiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, MalaysiaSchool of Physiology and Pharmacology, University of Bristol, Bristol, United KingdomSchool of Clinical Sciences, University of Bristol, Bristol, United Kingdom; Department of Physiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, MalaysiaIn response to an osmotic challenge, the synthesis of the antidiuretic hormone arginine vasopressin (AVP) increases in the hypothalamus, and this is accompanied by extension of the 3′ poly(A) tail of the AVP mRNA, and the up-regulation of the expression of RNA binding protein Caprin-2. Here we show that Caprin-2 binds to AVP mRNAs, and that lentiviral mediated shRNA knockdown of Caprin-2 in the osmotically stimulated hypothalamus shortens the AVP mRNA poly(A) tail at the same time as reducing transcript abundance. In a recapitulated in vitro system, we confirm that Caprin-2 over-expression enhances AVP mRNA abundance and poly(A) tail length. Importantly, we show that Caprin-2 knockdown in the hypothalamus decreases urine output and fluid intake, and increases urine osmolality, urine sodium concentration, and plasma AVP levels. Thus Caprin-2 controls physiological mechanisms that are essential for the body's response to osmotic stress.https://elifesciences.org/articles/09656polyadenylationosmoregulationvasopressinhypothalamus |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Agnieszka Konopacka Mingkwan Greenwood Su-Yi Loh Julian Paton David Murphy |
spellingShingle |
Agnieszka Konopacka Mingkwan Greenwood Su-Yi Loh Julian Paton David Murphy RNA binding protein Caprin-2 is a pivotal regulator of the central osmotic defense response eLife polyadenylation osmoregulation vasopressin hypothalamus |
author_facet |
Agnieszka Konopacka Mingkwan Greenwood Su-Yi Loh Julian Paton David Murphy |
author_sort |
Agnieszka Konopacka |
title |
RNA binding protein Caprin-2 is a pivotal regulator of the central osmotic defense response |
title_short |
RNA binding protein Caprin-2 is a pivotal regulator of the central osmotic defense response |
title_full |
RNA binding protein Caprin-2 is a pivotal regulator of the central osmotic defense response |
title_fullStr |
RNA binding protein Caprin-2 is a pivotal regulator of the central osmotic defense response |
title_full_unstemmed |
RNA binding protein Caprin-2 is a pivotal regulator of the central osmotic defense response |
title_sort |
rna binding protein caprin-2 is a pivotal regulator of the central osmotic defense response |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2015-11-01 |
description |
In response to an osmotic challenge, the synthesis of the antidiuretic hormone arginine vasopressin (AVP) increases in the hypothalamus, and this is accompanied by extension of the 3′ poly(A) tail of the AVP mRNA, and the up-regulation of the expression of RNA binding protein Caprin-2. Here we show that Caprin-2 binds to AVP mRNAs, and that lentiviral mediated shRNA knockdown of Caprin-2 in the osmotically stimulated hypothalamus shortens the AVP mRNA poly(A) tail at the same time as reducing transcript abundance. In a recapitulated in vitro system, we confirm that Caprin-2 over-expression enhances AVP mRNA abundance and poly(A) tail length. Importantly, we show that Caprin-2 knockdown in the hypothalamus decreases urine output and fluid intake, and increases urine osmolality, urine sodium concentration, and plasma AVP levels. Thus Caprin-2 controls physiological mechanisms that are essential for the body's response to osmotic stress. |
topic |
polyadenylation osmoregulation vasopressin hypothalamus |
url |
https://elifesciences.org/articles/09656 |
work_keys_str_mv |
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1721476588969656320 |