Role of m6A methylation in aging and Parkinson's disease

Using immunofluorescence imaging of fixed cells and tissue, along with biochemical analysis, we further investigated the expression of m6A regulatory enzymes—writer, N6-Adenosine-Methyltransferase Complex Catalytic Subunit (METTL3); reader, YTH N6-methyladenosine RNA-binding protein (YTHDF1); and eraser, fat mass and obesity-associated protein (FTO)—in the cortex, striatum, hippocampus, and cerebellum of Wt and Tg mice, as well as in primary cortical neuron cultures and observed a significant increase in the levels of YTHDF1 in Tg mice, however, the levels of METTL3 and FTO were similar when Tg mice were compared with Tg.

Interestingly, the m6A writer protein METTL3 was found to be present in both the nucleus and the neuronal post-synapse in neurons. Our findings suggest that m6A RNA methylation is plausibly associated with neurodegeneration and aging, and plays a significant role at the synapse.