Publication

Identification of an RNA Polymerase III Regulator Linked to Disease-Associated Protein Aggregation

Sin, O., de Jong, T., Mata-Cabana, A., Kudron, M., Zaini, M. A., Aprile, F. A., Seinstra, R. I., Stroo, E., Prins, R. W., Martineau, C. N., Wang, H. H., Hogewerf, W., Steinhof, A., Wanker, E. E., Vendruscolo, M., Calkhoven, C. F., Reinke, V., Guryev, V. & Nollen, E. A. A., 16-Mar-2017, In : Molecular Cell. 65, 6, p. 1096-1108 19 p.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Sin, O., de Jong, T., Mata-Cabana, A., Kudron, M., Zaini, M. A., Aprile, F. A., ... Nollen, E. A. A. (2017). Identification of an RNA Polymerase III Regulator Linked to Disease-Associated Protein Aggregation. Molecular Cell, 65(6), 1096-1108. https://doi.org/10.1016/j.molcel.2017.02.022

Author

Sin, Olga ; de Jong, Tristan ; Mata-Cabana, Alejandro ; Kudron, Michelle ; Zaini, Mohamad Amr ; Aprile, Francesco A. ; Seinstra, Renee I. ; Stroo, Esther ; Prins, Romeo Willinge ; Martineau, Celine N. ; Wang, Hai Hui ; Hogewerf, Wytse ; Steinhof, Anne ; Wanker, Erich E. ; Vendruscolo, Michele ; Calkhoven, Cornelis F. ; Reinke, Valerie ; Guryev, Victor ; Nollen, Ellen A. A. / Identification of an RNA Polymerase III Regulator Linked to Disease-Associated Protein Aggregation. In: Molecular Cell. 2017 ; Vol. 65, No. 6. pp. 1096-1108.

Harvard

Sin, O, de Jong, T, Mata-Cabana, A, Kudron, M, Zaini, MA, Aprile, FA, Seinstra, RI, Stroo, E, Prins, RW, Martineau, CN, Wang, HH, Hogewerf, W, Steinhof, A, Wanker, EE, Vendruscolo, M, Calkhoven, CF, Reinke, V, Guryev, V & Nollen, EAA 2017, 'Identification of an RNA Polymerase III Regulator Linked to Disease-Associated Protein Aggregation', Molecular Cell, vol. 65, no. 6, pp. 1096-1108. https://doi.org/10.1016/j.molcel.2017.02.022

Standard

Identification of an RNA Polymerase III Regulator Linked to Disease-Associated Protein Aggregation. / Sin, Olga; de Jong, Tristan; Mata-Cabana, Alejandro; Kudron, Michelle; Zaini, Mohamad Amr; Aprile, Francesco A.; Seinstra, Renee I.; Stroo, Esther; Prins, Romeo Willinge; Martineau, Celine N.; Wang, Hai Hui; Hogewerf, Wytse; Steinhof, Anne; Wanker, Erich E.; Vendruscolo, Michele; Calkhoven, Cornelis F.; Reinke, Valerie; Guryev, Victor; Nollen, Ellen A. A.

In: Molecular Cell, Vol. 65, No. 6, 16.03.2017, p. 1096-1108.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Sin O, de Jong T, Mata-Cabana A, Kudron M, Zaini MA, Aprile FA et al. Identification of an RNA Polymerase III Regulator Linked to Disease-Associated Protein Aggregation. Molecular Cell. 2017 Mar 16;65(6):1096-1108. https://doi.org/10.1016/j.molcel.2017.02.022


BibTeX

@article{b07f1a85811840eea7d294d002751a65,
title = "Identification of an RNA Polymerase III Regulator Linked to Disease-Associated Protein Aggregation",
abstract = "Protein aggregation is associated with age-related neurodegenerative disorders, such as Alzheimer's and polyglutamine diseases. As a causal relationship between protein aggregation and neurodegeneration remains elusive, understanding the cellular mechanisms regulating protein aggregation will help develop future treatments. To identify such mechanisms, we conducted a forward genetic screen in a C. elegans model of polyglutamine aggregation and identified the protein MOAG-2/LIR-3 as a driver of protein aggregation. In the absence of polyglutamine, MOAG-2/LIR-3 regulates the RNA polymerase III-associated transcription of small non-coding RNAs. This regulation is lost in the presence of polyglutamine, which mislocalizes MOAG-2/LIR-3 from the nucleus to the cytosol. We then show biochemically that MOAG-2/LIR-3 can also catalyze the aggregation of polyglutamine-expanded huntingtin. These results suggest that polyglutamine can induce an aggregation-promoting activity of MOAG-2/LIR-3 in the cytosol. The concept that certain aggregation-prone proteins can convert other endogenous proteins into drivers of aggregation and toxicity adds to the understanding of how cellular homeostasis can be deteriorated in protein misfolding diseases.",
keywords = "ZINC-FINGER PROTEINS, DIFFERENTIAL EXPRESSION ANALYSIS, CAENORHABDITIS-ELEGANS, C.-ELEGANS, TRANSCRIPTION FACTORS, HUNTINGTON-DISEASE, GENE-EXPRESSION, POSTTRANSLATIONAL MODIFICATIONS, NEURODEGENERATIVE DISEASES, POLYGLUTAMINE PROTEIN",
author = "Olga Sin and {de Jong}, Tristan and Alejandro Mata-Cabana and Michelle Kudron and Zaini, {Mohamad Amr} and Aprile, {Francesco A.} and Seinstra, {Renee I.} and Esther Stroo and Prins, {Romeo Willinge} and Martineau, {Celine N.} and Wang, {Hai Hui} and Wytse Hogewerf and Anne Steinhof and Wanker, {Erich E.} and Michele Vendruscolo and Calkhoven, {Cornelis F.} and Valerie Reinke and Victor Guryev and Nollen, {Ellen A. A.}",
note = "Copyright {\circledC} 2017 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2017",
month = "3",
day = "16",
doi = "10.1016/j.molcel.2017.02.022",
language = "English",
volume = "65",
pages = "1096--1108",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "CELL PRESS",
number = "6",

}

RIS

TY - JOUR

T1 - Identification of an RNA Polymerase III Regulator Linked to Disease-Associated Protein Aggregation

AU - Sin, Olga

AU - de Jong, Tristan

AU - Mata-Cabana, Alejandro

AU - Kudron, Michelle

AU - Zaini, Mohamad Amr

AU - Aprile, Francesco A.

AU - Seinstra, Renee I.

AU - Stroo, Esther

AU - Prins, Romeo Willinge

AU - Martineau, Celine N.

AU - Wang, Hai Hui

AU - Hogewerf, Wytse

AU - Steinhof, Anne

AU - Wanker, Erich E.

AU - Vendruscolo, Michele

AU - Calkhoven, Cornelis F.

AU - Reinke, Valerie

AU - Guryev, Victor

AU - Nollen, Ellen A. A.

N1 - Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2017/3/16

Y1 - 2017/3/16

N2 - Protein aggregation is associated with age-related neurodegenerative disorders, such as Alzheimer's and polyglutamine diseases. As a causal relationship between protein aggregation and neurodegeneration remains elusive, understanding the cellular mechanisms regulating protein aggregation will help develop future treatments. To identify such mechanisms, we conducted a forward genetic screen in a C. elegans model of polyglutamine aggregation and identified the protein MOAG-2/LIR-3 as a driver of protein aggregation. In the absence of polyglutamine, MOAG-2/LIR-3 regulates the RNA polymerase III-associated transcription of small non-coding RNAs. This regulation is lost in the presence of polyglutamine, which mislocalizes MOAG-2/LIR-3 from the nucleus to the cytosol. We then show biochemically that MOAG-2/LIR-3 can also catalyze the aggregation of polyglutamine-expanded huntingtin. These results suggest that polyglutamine can induce an aggregation-promoting activity of MOAG-2/LIR-3 in the cytosol. The concept that certain aggregation-prone proteins can convert other endogenous proteins into drivers of aggregation and toxicity adds to the understanding of how cellular homeostasis can be deteriorated in protein misfolding diseases.

AB - Protein aggregation is associated with age-related neurodegenerative disorders, such as Alzheimer's and polyglutamine diseases. As a causal relationship between protein aggregation and neurodegeneration remains elusive, understanding the cellular mechanisms regulating protein aggregation will help develop future treatments. To identify such mechanisms, we conducted a forward genetic screen in a C. elegans model of polyglutamine aggregation and identified the protein MOAG-2/LIR-3 as a driver of protein aggregation. In the absence of polyglutamine, MOAG-2/LIR-3 regulates the RNA polymerase III-associated transcription of small non-coding RNAs. This regulation is lost in the presence of polyglutamine, which mislocalizes MOAG-2/LIR-3 from the nucleus to the cytosol. We then show biochemically that MOAG-2/LIR-3 can also catalyze the aggregation of polyglutamine-expanded huntingtin. These results suggest that polyglutamine can induce an aggregation-promoting activity of MOAG-2/LIR-3 in the cytosol. The concept that certain aggregation-prone proteins can convert other endogenous proteins into drivers of aggregation and toxicity adds to the understanding of how cellular homeostasis can be deteriorated in protein misfolding diseases.

KW - ZINC-FINGER PROTEINS

KW - DIFFERENTIAL EXPRESSION ANALYSIS

KW - CAENORHABDITIS-ELEGANS

KW - C.-ELEGANS

KW - TRANSCRIPTION FACTORS

KW - HUNTINGTON-DISEASE

KW - GENE-EXPRESSION

KW - POSTTRANSLATIONAL MODIFICATIONS

KW - NEURODEGENERATIVE DISEASES

KW - POLYGLUTAMINE PROTEIN

U2 - 10.1016/j.molcel.2017.02.022

DO - 10.1016/j.molcel.2017.02.022

M3 - Article

VL - 65

SP - 1096

EP - 1108

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 6

ER -

ID: 40564822