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Series GSE8632 Query DataSets for GSE8632
Status Public on Mar 14, 2008
Title RNA binding activity of the recessive parkinsonism protein DJ-1
Organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by array
Summary Parkinson disease (PD) is a major neurodegenerative condition with several rare Mendelian forms. Oxidative stress and mitochondrial function have been implicated in the pathogenesis of PD but the molecular mechanism(s) involved in the degeneration of specific neuronal groups remains unclear. DJ-1 mutations are one cause of recessive parkinsonism, but this gene is also involved in cancer by promoting Ras signaling and suppressing PTEN-induced apoptosis. The specific function of DJ-1 is unclear, although it is responsive to oxidative stress and may play a role in the maintenance of mitochondria. Here we show that DJ-1 associates with specific RNA targets in cells and in the brain including mitochondrial genes, genes involved in glutathione metabolism and members of the PTEN/PI3K cascade. Pathogenic recessive mutants are deficient in this activity. We show that DJ-1 is sufficient for RNA binding at nanomolar concentrations in vitro and that there is some RNA sequence specificity to the association. Oxidative stress causes DJ-1 to dissociate from RNA. Using in vitro and in vivo models of mild oxidative stress, we show that DJ-1 normally suppresses translation in normal circumstances but allows translation after oxidative stress. We tested the hypothesis that these specific RNA targets are responsible for sensitivity to stress by exposing knockout flies to glutathione synthesis inhibitors and saw the predicted increased sensitivity in vivo. These data implicate a single mechanism for the pleiotropic effects of DJ-1 in different model systems, namely that the protein binds and regulates specific groups of RNA targets in an oxidationdependent manner. Furthermore, these results suggest how a small protein might both be an upstream regulator of processes important in parkinsonism and be a modifier of cancer-related processes.
Keywords: Immunoprecipitated RNA comparisons
 
Overall design 6-8 biological replicates of RNA immunoprecipitated with DJ-1 protein was compared to RNA isolated with a nonspecific IgG control antibody in human cells, or to nonspecific RNA isolated with the DJ-1 antibody from KO mouse brains.
 
Contributor(s) van der Brug MP, Blackinton J, Chandran J, Hao L, Lal A, Gorospe M, Cookson MR
Citation(s) 18626009
Submission date Jul 30, 2007
Last update date Mar 17, 2012
Contact name J Raphael Gibbs
E-mail(s) gibbsr@mail.nih.gov
Organization name National Institutue on Aging, NIH
Department Computational Biology Core
Lab Laboratory of Neurogenetics
Street address 35 Convent Drive, Bldg 35/1A1015, MSC3707
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
 
Platforms (2)
GPL2507 Sentrix Human-6 Expression BeadChip
GPL4234 Sentrix Mouse-6 Expression BeadChip
Samples (4)
GSM213760 Human DJ-1 IP
GSM213761 Human IgG IP
GSM213769 WT Mouse DJ-1 IP
Relations
BioProject PRJNA101815

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE8632_RAW.tar 12.4 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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