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

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

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  • Cite this

    Repici, M., Hassanjani, M., Maddison, D. C., Garção, P., Cimini, S., Patel, B., Szegö, É. M., Straatman, K. R., Lilley, K. S., Borsello, T., Outeiro, T. F., Panman, L., & 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