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Lookup NU author(s): Professor Tiago OuteiroORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2026.N6-methyladenosine (m6A) is the most abundant transcriptional modification in eukaryotic RNA, regulating RNA fate. While the functions of m6A in the development of the mammalian brain have been extensively studied, its role in synaptic plasticity, and brain function remain underexplored. The involvement of this modification in Parkinson’s disease and other synucleinopathies has only recently been studied, and needs further investigation. Here, we investigated the m6A epitranscriptome using MeRIP-seq in A30P-aSyn transgenic mice (aSyn Tg). We observed hypermethylation of synaptic genes in young aSyn Tg mice compared to age-matched control mice. The methylation was reduced during ageing. Using immunofluorescence imaging and biochemical analysis, we further investigated the levels and distribution of m6A regulatory enzymes—writer, METTL3, reader, YTHDF1, and eraser, FTO, in the cortex, striatum, hippocampus, and cerebellum of aSyn Tg and control mice, and in primary cortical neuronal cultures. While the levels of these proteins were similar, METTL3 was found in the nucleus and in the post-synaptic compartment in neurons, suggesting it may play a role in methylation at the post-synapse. Our findings suggest that alterations in the regulation of m6A RNA methylation may be associated with neurodegeneration and ageing and it may play a significant role at the synapse.
Author(s): Chopra A, Xylaki M, Yin F, Castro-Hernandez R, Merghani M, Grande V, Mollenhauer B, Fischer A, Outeiro TF
Publication type: Article
Publication status: Published
Journal: npj Parkinson's Disease
Year: 2026
Volume: 12
Issue: 1
Online publication date: 06/05/2026
Acceptance date: 12/04/2026
Date deposited: 09/06/2026
ISSN (electronic): 2373-8057
Publisher: Nature Research
URL: https://doi.org/10.1038/s41531-026-01362-3
DOI: 10.1038/s41531-026-01362-3
Data Access Statement: The datasets used and/or analysed during the current study are available from the corresponding author upon reasonable request. All raw data files for MeRIP-seq are available on the GEO database (GSE275432). To review GEO accession GSE275432 on https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE275432, enter token otebmkqmxdkrlot into the box.
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