RNA binding protein Caprin-2 is a pivotal regulator of the central osmotic defense response

Agnieszka Konopacka; Mingkwan Greenwood; Su Yi Loh; Julian Paton; David Murphy

doi:10.7554/eLife.09656

RNA binding protein Caprin-2 is a pivotal regulator of the central osmotic defense response

Agnieszka Konopacka, Mingkwan Greenwood, Su Yi Loh, Julian Paton, David Murphy

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Abstract

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.

Original language	English
Article number	e09656
Number of pages	23
Journal	eLife
Volume	4
DOIs	https://doi.org/10.7554/eLife.09656
Publication status	Published - 12 Nov 2015

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elife09656
This is the final published version of the article (version of record). It first appeared online via eLife Sciences Publications at http://dx.doi.org/10.7554/eLife.09656. Please refer to any applicable terms of use of the publisher.
Final published version, 3.78 MBLicence: CC BY

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Bilateral BBSRC-FAPESP: Behavioural and neuroendocrine mechanisms regulating hydromineral homeostasis - a lifelong perspective
Murphy, D. (Principal Investigator)
10/01/13 → 10/05/16
Project: Research
GENE NETWORKS INVOLVED IN HYPOTHALAMIC PLASTICITY IN RESPONSE TO DEHYDRATION; ASSESSING THE IN VIVO FUNCTIONS OF CANDIDATE NODAL GENES.
Murphy, D. (Principal Investigator)
9/03/09 → 9/05/12
Project: Research

Professor David Murphy
- D.Murphybristol.acuk
- School of Physiology, Pharmacology & Neuroscience - Professor of Experimental Medicine
- Molecular Neuroendocrinology Research Group
- Bristol Neuroscience
Person: Academic , Member, Group lead

Cite this

@article{1d05deb9984b498ebc9c7bdde5034ddd,

title = "RNA binding protein Caprin-2 is a pivotal regulator of the central osmotic defense response",

abstract = "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.",

author = "Agnieszka Konopacka and Mingkwan Greenwood and Loh, \{Su Yi\} and Julian Paton and David Murphy",

year = "2015",

month = nov,

day = "12",

doi = "10.7554/eLife.09656",

language = "English",

volume = "4",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications Ltd",

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TY - JOUR

T1 - RNA binding protein Caprin-2 is a pivotal regulator of the central osmotic defense response

AU - Konopacka, Agnieszka

AU - Greenwood, Mingkwan

AU - Loh, Su Yi

AU - Paton, Julian

AU - Murphy, David

PY - 2015/11/12

Y1 - 2015/11/12

N2 - 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.

AB - 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.

U2 - 10.7554/eLife.09656

DO - 10.7554/eLife.09656

M3 - Article (Academic Journal)

C2 - 26559902

SN - 2050-084X

VL - 4

JO - eLife

JF - eLife

M1 - e09656

ER -

RNA binding protein Caprin-2 is a pivotal regulator of the central osmotic defense response

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Projects

Bilateral BBSRC-FAPESP: Behavioural and neuroendocrine mechanisms regulating hydromineral homeostasis - a lifelong perspective

GENE NETWORKS INVOLVED IN HYPOTHALAMIC PLASTICITY IN RESPONSE TO DEHYDRATION; ASSESSING THE IN VIVO FUNCTIONS OF CANDIDATE NODAL GENES.

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Professor David Murphy

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