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

Lookup NU author(s): Professor Tiago Outeiro

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2018 The Author(s) 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.


Publication metadata

Author(s): Repici M, Hassanjani M, Maddison DC, Garcao P, Cimini S, Patel B, Szego EM, Straatman KR, Lilley KS, Borsello T, Outeiro TF, Panman L, Giorgini F

Publication type: Article

Publication status: Published

Journal: Molecular Neurobiology

Year: 2019

Volume: 56

Issue: 1

Pages: 61-77

Print publication date: 01/01/2019

Online publication date: 19/04/2018

Acceptance date: 11/04/2018

Date deposited: 31/05/2018

ISSN (print): 0893-7648

ISSN (electronic): 1559-1182

Publisher: Springer

URL: https://doi.org/10.1007/s12035-018-1084-y

DOI: 10.1007/s12035-018-1084-y


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