The Parkinson's Disease-Linked Protein DJ-1 Associates with Cytoplasmic mRNP Granules During Stress and Neurodegeneration.
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.
['Repici|Mariaelena|M|', 'Hassanjani|Mahdieh|M|', 'Maddison|Daniel C|DC|', 'Garção|Pedro|P|', 'Cimini|Sara|S|', 'Patel|Bhavini|B|', 'Szegö|Éva M|ÉM|', 'Straatman|Kornelis R|KR|', 'Lilley|Kathryn S|KS|', 'Borsello|Tiziana|T|', 'Outeiro|Tiago F|TF|', 'Panman|Lia|L|', 'Giorgini|Flaviano|F|http://orcid.org/0000-0001-7881-9508']
D000818:Animals D003594:Cytoplasmic Granules D057809:HEK293 Cells D006801:Humans D051379:Mice D016202:N-Methylaspartate D009410:Nerve Degeneration D009474:Neurons D009997:Osmotic Pressure D018384:Oxidative Stress D010300:Parkinson Disease D011485:Protein Binding D000071617:Protein Deglycase DJ-1 D051381:Rats D012261:Ribonucleoproteins D013312:Stress, Physiological
DJ-1 Stress granules Parkinson’s disease RNA-binding proteins