RT Journal Article SR Electronic T1 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 JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.03.25.437102 DO 10.1101/2021.03.25.437102 A1 Hui Yung Chin A1 Michael Lardelli A1 Lyndsey Collins-Praino A1 Karissa Barthelson YR 2021 UL http://biorxiv.org/content/early/2021/03/26/2021.03.25.437102.abstract AB 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.Competing Interest StatementThe authors have declared no competing interest.PDParkinson’s diseaseIREIron responsive elementHQHigh qualityUTRsuntranslatedGSHglutathioneSNc DAsubstantia nigra pars compacta dopaminergic neuronsETCElectron transport chainROSReactive oxygen speciesIRP1Iron regulatory proteins 1IRP2Iron regulatory proteins 2mRNAMessenger ribonucleic acidADAlzheimer’s diseaseRNA-seqRNA sequencingGSEAgene set enrichment analysisalas 2Delta-aminolevulinate synthase 2FDRfalse discovery rate