The Parkinson's Disease-Linked Protein DJ-1 Associates with Cytoplasmic mRNP Granules During Stress and Neurodegeneration

Mariaelena Repici, Mahdieh Hassanjani, Daniel C Maddison, Pedro Garção, Sara Cimini, Bhavini Patel, Éva M Szegö, Kornelis R Straatman, Kathryn S Lilley, Tiziana Borsello, Tiago F Outeiro, Lia Panman, Flaviano Giorgini

Research output: Contribution to journalArticle

Abstract

Mutations in the gene encoding DJ-1 are associated with autosomal recessive forms of Parkinson's disease (PD). DJ-1 plays a role in protection from oxidative stress, but how it functions as an "upstream" oxidative stress sensor and whether this relates to PD is still unclear. Intriguingly, DJ-1 may act as an RNA binding protein associating with specific mRNA transcripts in the human brain. Moreover, we previously reported that the yeast DJ-1 homolog Hsp31 localizes to stress granules (SGs) after glucose starvation, suggesting a role for DJ-1 in RNA dynamics. Here, we report that DJ-1 interacts with several SG components in mammalian cells and localizes to SGs, as well as P-bodies, upon induction of either osmotic or oxidative stress. By purifying the mRNA associated with DJ-1 in mammalian cells, we detected several transcripts and found that subpopulations of these localize to SGs after stress, suggesting that DJ-1 may target specific mRNAs to mRNP granules. Notably, we find that DJ-1 associates with SGs arising from N-methyl-D-aspartate (NMDA) excitotoxicity in primary neurons and parkinsonism-inducing toxins in dopaminergic cell cultures. Thus, our results indicate that DJ-1 is associated with cytoplasmic RNA granules arising during stress and neurodegeneration, providing a possible link between DJ-1 and RNA dynamics which may be relevant for PD pathogenesis.

Original languageEnglish
Pages (from-to)61-77
Number of pages17
JournalMolecular Neurobiology
Volume56
Issue number1
Early online date19 Apr 2018
DOIs
Publication statusPublished - 1 Jan 2019

Fingerprint

Cytoplasmic Granules
Parkinson Disease
Oxidative Stress
RNA
Messenger RNA
RNA-Binding Proteins
Osmotic Pressure
N-Methylaspartate
Starvation
Cell Culture Techniques
Yeasts
Neurons
Glucose
Mutation
messenger ribonucleoprotein
Protein Deglycase DJ-1
Brain
Genes

Bibliographical note

© The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Keywords

  • DJ-1
  • Parkinson’s disease
  • RNA-binding proteins
  • Stress granules

Cite this

Repici, M., Hassanjani, M., Maddison, D. C., Garção, P., Cimini, S., Patel, B., ... Giorgini, F. (2019). The Parkinson's Disease-Linked Protein DJ-1 Associates with Cytoplasmic mRNP Granules During Stress and Neurodegeneration. Molecular Neurobiology, 56(1), 61-77. https://doi.org/10.1007/s12035-018-1084-y
Repici, Mariaelena ; Hassanjani, Mahdieh ; Maddison, Daniel C ; Garção, Pedro ; Cimini, Sara ; Patel, Bhavini ; Szegö, Éva M ; Straatman, Kornelis R ; Lilley, Kathryn S ; Borsello, Tiziana ; Outeiro, Tiago F ; Panman, Lia ; Giorgini, Flaviano. / The Parkinson's Disease-Linked Protein DJ-1 Associates with Cytoplasmic mRNP Granules During Stress and Neurodegeneration. In: Molecular Neurobiology. 2019 ; Vol. 56, No. 1. pp. 61-77.
@article{010406fbdbe348368a487c31e0b10711,
title = "The Parkinson's Disease-Linked Protein DJ-1 Associates with Cytoplasmic mRNP Granules During Stress and Neurodegeneration",
abstract = "Mutations in the gene encoding DJ-1 are associated with autosomal recessive forms of Parkinson's disease (PD). DJ-1 plays a role in protection from oxidative stress, but how it functions as an {"}upstream{"} oxidative stress sensor and whether this relates to PD is still unclear. Intriguingly, DJ-1 may act as an RNA binding protein associating with specific mRNA transcripts in the human brain. Moreover, we previously reported that the yeast DJ-1 homolog Hsp31 localizes to stress granules (SGs) after glucose starvation, suggesting a role for DJ-1 in RNA dynamics. Here, we report that DJ-1 interacts with several SG components in mammalian cells and localizes to SGs, as well as P-bodies, upon induction of either osmotic or oxidative stress. By purifying the mRNA associated with DJ-1 in mammalian cells, we detected several transcripts and found that subpopulations of these localize to SGs after stress, suggesting that DJ-1 may target specific mRNAs to mRNP granules. Notably, we find that DJ-1 associates with SGs arising from N-methyl-D-aspartate (NMDA) excitotoxicity in primary neurons and parkinsonism-inducing toxins in dopaminergic cell cultures. Thus, our results indicate that DJ-1 is associated with cytoplasmic RNA granules arising during stress and neurodegeneration, providing a possible link between DJ-1 and RNA dynamics which may be relevant for PD pathogenesis.",
keywords = "DJ-1, Parkinson’s disease, RNA-binding proteins, Stress granules",
author = "Mariaelena Repici and Mahdieh Hassanjani and Maddison, {Daniel C} and Pedro Gar{\cc}{\~a}o and Sara Cimini and Bhavini Patel and Szeg{\"o}, {{\'E}va M} and Straatman, {Kornelis R} and Lilley, {Kathryn S} and Tiziana Borsello and Outeiro, {Tiago F} and Lia Panman and Flaviano Giorgini",
note = "{\circledC} The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/s12035-018-1084-y",
language = "English",
volume = "56",
pages = "61--77",
number = "1",

}

Repici, M, Hassanjani, M, Maddison, DC, Garção, P, Cimini, S, Patel, B, Szegö, ÉM, Straatman, KR, Lilley, KS, Borsello, T, Outeiro, TF, Panman, L & Giorgini, F 2019, 'The Parkinson's Disease-Linked Protein DJ-1 Associates with Cytoplasmic mRNP Granules During Stress and Neurodegeneration', Molecular Neurobiology, vol. 56, no. 1, pp. 61-77. https://doi.org/10.1007/s12035-018-1084-y

The Parkinson's Disease-Linked Protein DJ-1 Associates with Cytoplasmic mRNP Granules During Stress and Neurodegeneration. / Repici, Mariaelena; Hassanjani, Mahdieh; Maddison, Daniel C; Garção, Pedro; Cimini, Sara; Patel, Bhavini; Szegö, Éva M; Straatman, Kornelis R; Lilley, Kathryn S; Borsello, Tiziana; Outeiro, Tiago F; Panman, Lia; Giorgini, Flaviano.

In: Molecular Neurobiology, Vol. 56, No. 1, 01.01.2019, p. 61-77.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The Parkinson's Disease-Linked Protein DJ-1 Associates with Cytoplasmic mRNP Granules During Stress and Neurodegeneration

AU - Repici, Mariaelena

AU - Hassanjani, Mahdieh

AU - Maddison, Daniel C

AU - Garção, Pedro

AU - Cimini, Sara

AU - Patel, Bhavini

AU - Szegö, Éva M

AU - Straatman, Kornelis R

AU - Lilley, Kathryn S

AU - Borsello, Tiziana

AU - Outeiro, Tiago F

AU - Panman, Lia

AU - Giorgini, Flaviano

N1 - © The Author(s) 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Mutations in the gene encoding DJ-1 are associated with autosomal recessive forms of Parkinson's disease (PD). DJ-1 plays a role in protection from oxidative stress, but how it functions as an "upstream" oxidative stress sensor and whether this relates to PD is still unclear. Intriguingly, DJ-1 may act as an RNA binding protein associating with specific mRNA transcripts in the human brain. Moreover, we previously reported that the yeast DJ-1 homolog Hsp31 localizes to stress granules (SGs) after glucose starvation, suggesting a role for DJ-1 in RNA dynamics. Here, we report that DJ-1 interacts with several SG components in mammalian cells and localizes to SGs, as well as P-bodies, upon induction of either osmotic or oxidative stress. By purifying the mRNA associated with DJ-1 in mammalian cells, we detected several transcripts and found that subpopulations of these localize to SGs after stress, suggesting that DJ-1 may target specific mRNAs to mRNP granules. Notably, we find that DJ-1 associates with SGs arising from N-methyl-D-aspartate (NMDA) excitotoxicity in primary neurons and parkinsonism-inducing toxins in dopaminergic cell cultures. Thus, our results indicate that DJ-1 is associated with cytoplasmic RNA granules arising during stress and neurodegeneration, providing a possible link between DJ-1 and RNA dynamics which may be relevant for PD pathogenesis.

AB - Mutations in the gene encoding DJ-1 are associated with autosomal recessive forms of Parkinson's disease (PD). DJ-1 plays a role in protection from oxidative stress, but how it functions as an "upstream" oxidative stress sensor and whether this relates to PD is still unclear. Intriguingly, DJ-1 may act as an RNA binding protein associating with specific mRNA transcripts in the human brain. Moreover, we previously reported that the yeast DJ-1 homolog Hsp31 localizes to stress granules (SGs) after glucose starvation, suggesting a role for DJ-1 in RNA dynamics. Here, we report that DJ-1 interacts with several SG components in mammalian cells and localizes to SGs, as well as P-bodies, upon induction of either osmotic or oxidative stress. By purifying the mRNA associated with DJ-1 in mammalian cells, we detected several transcripts and found that subpopulations of these localize to SGs after stress, suggesting that DJ-1 may target specific mRNAs to mRNP granules. Notably, we find that DJ-1 associates with SGs arising from N-methyl-D-aspartate (NMDA) excitotoxicity in primary neurons and parkinsonism-inducing toxins in dopaminergic cell cultures. Thus, our results indicate that DJ-1 is associated with cytoplasmic RNA granules arising during stress and neurodegeneration, providing a possible link between DJ-1 and RNA dynamics which may be relevant for PD pathogenesis.

KW - DJ-1

KW - Parkinson’s disease

KW - RNA-binding proteins

KW - Stress granules

UR - https://link.springer.com/article/10.1007%2Fs12035-018-1084-y

UR - http://www.scopus.com/inward/record.url?scp=85045734709&partnerID=8YFLogxK

U2 - 10.1007/s12035-018-1084-y

DO - 10.1007/s12035-018-1084-y

M3 - Article

C2 - 29675578

VL - 56

SP - 61

EP - 77

IS - 1

ER -

Repici M, Hassanjani M, Maddison DC, Garção P, Cimini S, Patel B et al. The Parkinson's Disease-Linked Protein DJ-1 Associates with Cytoplasmic mRNP Granules During Stress and Neurodegeneration. Molecular Neurobiology. 2019 Jan 1;56(1):61-77. https://doi.org/10.1007/s12035-018-1084-y