The Parkinson's disease-linked protein dj-1 associates with cytoplasmic mrnp granules during stress and neurodegeneration.

Repici, Mariaelena, Hassanjani, Mahdieh, Maddison, Daniel C. ORCID: https://orcid.org/0000-0003-3038-1687, Garção, Pedro, Cimini, Sara, Patel, Bhavini, Szegö, Éva M., Straatman, Kornelis R., Lilley, Kathryn S., Borsello, Tiziana, Outeiro, Tiago F., Panman, Lia and Giorgini, Flaviano 2019. The Parkinson's disease-linked protein dj-1 associates with cytoplasmic mrnp granules during stress and neurodegeneration. Molecular Neurobiology 56 (1) , pp. 61-77. 10.1007/s12035-018-1084-y

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Additional Information:	This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http:// creativecommons.org/licenses/by/4.0/),
Publisher:	Springer
ISSN:	0893-7648
Date of First Compliant Deposit:	4 August 2022
Date of Acceptance:	11 April 2018
Last Modified:	06 Jan 2024 04:40
URI:	https://orca.cardiff.ac.uk/id/eprint/151327

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