METTL14 is decreased and regulates m6A modification of α‐synuclein in Parkinson's disease

This study provides novel evidence that the levels of m6A were significantly decreased in the peripheral blood of Parkinson's disease, and METTL14 was the main factor involved in abnormal m6A modification, and has the potential to be a novel diagnostic biomarker for PD. Mechanism experiments showed that METTL14 catalyze the m6A modification on α-syn mRNA through binding to the m6A motif in the CDS regions of α-syn mRNA, and need YTHDF2 recognizing m6A -modified α-syn mRNA to promote α-syn degradation. AbstractN6-methyladenosine (m6A), an emerging modification of messenger RNA, has been implicated in many biological processes. However, its role in Parkinson's disease (PD) remains largely unknown. Here, we investigated the role of m6A modification and its underlying mechanism in PD. First, 86 individuals with PD and 86 healthy controls were recruited from a pilot multicenter cohort. Levels of m6A and its modulators in peripheral blood mononuclear cells of patients with PD and controls were measured using an m6A RNA methylation quantification kit and quantitative real-time PCR. The underlying mechanism of m6A modification in PD was investigated in vitro through RNA immunoprecipitation assay, RNA stability assay, gene silencing or overexpression, western blot, and confocal immunoassay. The results show that mRNA levels of m6A,METTL3, METTL14, andYTHDF2 in patients with PD were significantly lower than in healthy controls, and METTL14 was the main factor involved in abnormal m...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research