Loss of park7 activity has differential effects on expression of iron responsive element (IRE) gene sets in the brain transcriptome in a zebrafish model of Parkinson’s disease

Molecular Brain

Karissa Barthelson¹  Michael Lardelli¹  Hui Yung Chin¹  Lyndsey Collins-Praino² 

[1] Alzheimer’s Disease Genetics Laboratory, School of Biological Sciences, University of Adelaide, North Terrace, 5005, Adelaide, SA, Australia;Department of Biomedical Sciences, Adelaide Medical School, University of Adelaide, Frome Rd, 5005, Adelaide, SA, Australia;

关键词: DJ-1;    PARK7;    Parkinson disease;    Zebrafish;    RNA-seq;    Enrichment analysis;    Iron dyshomeostasis;   

DOI  :  10.1186/s13041-021-00792-9

来源: Springer

【 摘 要 】

Mutation of the gene PARK7 (DJ1) causes monogenic autosomal recessive Parkinson’s disease (PD) in humans. Subsequent alterations of PARK7 protein function lead to mitochondrial dysfunction, a major element in PD pathology. Homozygous mutants for the PARK7-orthologous genes in zebrafish, park7, show changes to gene expression in the oxidative phosphorylation pathway, supporting that disruption of energy production is a key feature of neurodegeneration in PD. Iron is critical for normal mitochondrial function, and we have previously used bioinformatic analysis of IRE-bearing transcripts in brain transcriptomes to find evidence supporting the existence of iron dyshomeostasis in Alzheimer’s disease. Here, we analysed IRE-bearing transcripts in the transcriptome data from homozygous park7−/− mutant zebrafish brains. We found that the set of genes with “high quality” IREs in their 5′ untranslated regions (UTRs, the HQ5′IRE gene set) was significantly altered in these 4-month-old park7−/− brains. However, sets of genes with IREs in their 3′ UTRs appeared unaffected. The effects on HQ5′IRE genes are possibly driven by iron dyshomeostasis and/or oxidative stress, but illuminate the existence of currently unknown mechanisms with differential overall effects on 5′ and 3′ IREs.

【 授权许可】

CC BY