HSP90 protein stabilizes unloaded Argonaute complexes and microscopic P-bodies in human cells

Michael Johnston; Marie-Claude Geoffroy; Andrew Sobala; Ron Hay; Gyorgy Hutvagner

doi:10.1091/mbc.E09-10-0885

HSP90 protein stabilizes unloaded Argonaute complexes and microscopic P-bodies in human cells

Michael Johnston, Marie-Claude Geoffroy, Andrew Sobala, Ron Hay, Gyorgy Hutvagner

Research output: Contribution to journal › Article › peer-review

143 Citations (Scopus)

Abstract

Key components of the miRNA-mediated gene regulation pathway are localized in cytoplasmic processing bodies (P-bodies). Mounting evidence suggests that the presence of microscopic P-bodies are not always required for miRNA-mediated gene regulation. Here we have shown that geldanamycin, a well-characterized HSP90 inhibitor, abolishes P-bodies and significantly reduces Argonaute and GW182 protein levels but does not affect the miRNA level and the efficiency of miRNA-mediated gene repression; however, it significantly impairs siRNA loading and the efficacy of exogenous siRNA. Our data suggests that HSP90 protein chaperones Argonautes before binding RNA and may facilitate efficient loading of small RNA.

Original language	English
Pages (from-to)	1462-1469
Number of pages	8
Journal	Molecular Biology of the Cell
Volume	21
Issue number	9
DOIs	https://doi.org/10.1091/mbc.E09-10-0885
Publication status	Published - 1 May 2010

Keywords

MEDIATED TRANSLATIONAL REPRESSION
MESSENGER-RNA DECAY
LET-7 MICRORNA
GW/P-BODIES
PAZ DOMAIN
GW182
MIRNA
TARGET
REQUIRES
BINDING

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title = "HSP90 protein stabilizes unloaded Argonaute complexes and microscopic P-bodies in human cells",

abstract = "Key components of the miRNA-mediated gene regulation pathway are localized in cytoplasmic processing bodies (P-bodies). Mounting evidence suggests that the presence of microscopic P-bodies are not always required for miRNA-mediated gene regulation. Here we have shown that geldanamycin, a well-characterized HSP90 inhibitor, abolishes P-bodies and significantly reduces Argonaute and GW182 protein levels but does not affect the miRNA level and the efficiency of miRNA-mediated gene repression; however, it significantly impairs siRNA loading and the efficacy of exogenous siRNA. Our data suggests that HSP90 protein chaperones Argonautes before binding RNA and may facilitate efficient loading of small RNA.",

keywords = "MEDIATED TRANSLATIONAL REPRESSION, MESSENGER-RNA DECAY, LET-7 MICRORNA, GW/P-BODIES, PAZ DOMAIN, GW182, MIRNA, TARGET, REQUIRES, BINDING",

author = "Michael Johnston and Marie-Claude Geoffroy and Andrew Sobala and Ron Hay and Gyorgy Hutvagner",

year = "2010",

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doi = "10.1091/mbc.E09-10-0885",

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publisher = "American Society for Cell Biology",

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T1 - HSP90 protein stabilizes unloaded Argonaute complexes and microscopic P-bodies in human cells

AU - Johnston, Michael

AU - Geoffroy, Marie-Claude

AU - Sobala, Andrew

AU - Hay, Ron

AU - Hutvagner, Gyorgy

PY - 2010/5/1

Y1 - 2010/5/1

N2 - Key components of the miRNA-mediated gene regulation pathway are localized in cytoplasmic processing bodies (P-bodies). Mounting evidence suggests that the presence of microscopic P-bodies are not always required for miRNA-mediated gene regulation. Here we have shown that geldanamycin, a well-characterized HSP90 inhibitor, abolishes P-bodies and significantly reduces Argonaute and GW182 protein levels but does not affect the miRNA level and the efficiency of miRNA-mediated gene repression; however, it significantly impairs siRNA loading and the efficacy of exogenous siRNA. Our data suggests that HSP90 protein chaperones Argonautes before binding RNA and may facilitate efficient loading of small RNA.

AB - Key components of the miRNA-mediated gene regulation pathway are localized in cytoplasmic processing bodies (P-bodies). Mounting evidence suggests that the presence of microscopic P-bodies are not always required for miRNA-mediated gene regulation. Here we have shown that geldanamycin, a well-characterized HSP90 inhibitor, abolishes P-bodies and significantly reduces Argonaute and GW182 protein levels but does not affect the miRNA level and the efficiency of miRNA-mediated gene repression; however, it significantly impairs siRNA loading and the efficacy of exogenous siRNA. Our data suggests that HSP90 protein chaperones Argonautes before binding RNA and may facilitate efficient loading of small RNA.

KW - MEDIATED TRANSLATIONAL REPRESSION

KW - MESSENGER-RNA DECAY

KW - LET-7 MICRORNA

KW - GW/P-BODIES

KW - PAZ DOMAIN

KW - GW182

KW - MIRNA

KW - TARGET

KW - REQUIRES

KW - BINDING

U2 - 10.1091/mbc.E09-10-0885

DO - 10.1091/mbc.E09-10-0885

M3 - Article

C2 - 20237157

SN - 1059-1524

VL - 21

SP - 1462

EP - 1469

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

IS - 9

ER -

HSP90 protein stabilizes unloaded Argonaute complexes and microscopic P-bodies in human cells

Abstract

Keywords

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