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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Main Authors: Agnieszka Konopacka, Mingkwan Greenwood, Su-Yi Loh, Julian Paton, David Murphy
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2015-11-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/09656
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spelling 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
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AT suyiloh rnabindingproteincaprin2isapivotalregulatorofthecentralosmoticdefenseresponse
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