Objective: To identify RNA editing alterations associated with Parkinson’s disease (PD) in the Dorsal Motor Nucleus of the Vagus (DMV), Substantia Nigra (SN), and Cingulate Gyrus (CG).
Background: RNA editing is the post-transcriptional modification of individual bases, and disrupted RNA editing has been observed in multiple neurological and neurodegenerative disorders. However, the RNA editing landscape in PD has yet to be characterized.
Method: Whole transcriptome RNA sequencing was performed on tissue from the DMV, SN, and CG of 17 cases and 16 age and sex matched controls. REDItools software was used to identify and filter candidate editing events, and differentially edited sites were identified using a logistical regression, correcting for covariates. Differentially edited genes were analyzed for Gene Ontology term enrichment. Differentially edited sites affecting miRNA binding sites were identified using TargetScan, and sites resulting in coding changes were identified using PROVEAN.
Results: We identified 61,534 total combined editing events meeting quality control criteria in samples from CG, DMV, and SN. 209 sites in 111 genes were differentially edited between PD cases and controls in DMV and 598 sites in 228 genes were differentially edited in SN, with 43 genes differentially edited in both DMV and SN. No sites were differentially edited in CG. One differentially edited site in DMV and four in SN were predicted to result in damaging amino acid changes, including ANK2, which lies near the PD GWAS-associated locus on chromosome 4. In addition, miRNA binding was predicted to be disrupted at a differentially edited site in the MARCKS gene in both SN and DMV. Differentially edited sites were enriched in genes in mitochondrial and manganese-binding biological processes [table1] .
Conclusion: These results indicate that RNA editing is dysregulated in pathways known to contribute to PD, including mitochondrial function and manganese binding. This provides evidence of a post-transcriptional program contributing to the underlying complexity of PD pathophysiology and suggests that post-transcriptional dysregulation may contribute broadly to the pathogenesis of PD.
To cite this abstract in AMA style:
A. Thele, O. Gardner, J. Vance, A. Griswold, J. Young, M. Pericak-Vance, W. Scott, E. Martin, W. Wang, D. Dykxhoorn, C. Petito, G. Beecham, D. Mash, S. Sivasankaran. RNA Editing in Parkinson’s Disease Shows Changes in Mitochondrial and Manganese-Binding Pathways in Multiple Brain Regions [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/rna-editing-in-parkinsons-disease-shows-changes-in-mitochondrial-and-manganese-binding-pathways-in-multiple-brain-regions/. Accessed June 15, 2025.« Back to MDS Virtual Congress 2021
MDS Abstracts - https://www.mdsabstracts.org/abstract/rna-editing-in-parkinsons-disease-shows-changes-in-mitochondrial-and-manganese-binding-pathways-in-multiple-brain-regions/