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bioRxiv · 10.1101/2021.03.25.437102

Differential effects of loss of park7 activity on Iron Responsive Element (IRE) gene sets: Implications for the role of iron dyshomeostasis in the pathophysiology of Parkinson's disease

Chin, H. Y.·Lardelli, M.·Collins-Praino, L.·Barthelson, K.
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Abstract

Mutation of the gene PARK7 (DJ1) causes monogenic autosomal recessive Parkinsons 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 Alzheimers 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 HQ5IRE 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 HQ5IRE 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.

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Chin, H. Y., Lardelli, M., Collins-Praino, L., Barthelson, K.. 2021-03-27. Differential effects of loss of park7 activity on Iron Responsive Element (IRE) gene sets: Implications for the role of iron dyshomeostasis in the pathophysiology of Parkinson's disease. https://doi.org/10.1101/2021.03.25.437102

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