The Potential Regulation of A-to-I RNA editing on Genes in Parkinson’s Disease

Abstract

ABSTRACTParkinson’s disease (PD), the second most common neurodegenerative disorder, was characterized by alpha-synuclein pathology and dopaminergic neuron degeneration. In previous studies, multiple genes have been demonstrated to involve in the regulations of these two processes, including EIF2AK2, AGO2, MCL1, EEF1A1, and AIMP2. The molecular mechanisms to mediate the transcript diversity of these genetic biomarkers were important to understand neurodegenerative pathogenesis and helpful for treatment design. In this study, we analyzed 372 PD patients to identify 9,897 A-to-I RNA editing events probably responsible for the controls of 6,286 genes. Due to the most potentially trans-regulatory associations between RNA editing events and genes, we tried to explain one possible pathway from the view of disturbed miRNA regulations on genes due to A-to-I RNA editing events. Specifically, we identified 72 RNA editing events probably interfering in miRNA regulations on their host genes, eight RNA editing events possibly altering miRNA competitions between their host genes and 1,146 other genes, and one RNA editing event modifying miRNA seed regions to potentially disturb its regulations on four genes. All the analyses revealed 25 RNA editing biomarkers in Parkinson’s pathogenesis through probably interfering in miRNA degradations on 133 PD-related genes.