Transcriptome-wide regulation of folate on neural mRNA mA methylome via carbon metabolism in Drosophila and mammals.

Increasing evidence shows that folate can regulate neural gene function through DNA modification, while regulatory roles of folate in neural RNA modification remain largely unknown. Here we show that folate treatment significantly increased Drosophila mRNA mA levels. RNA methylation analysis indicates that carbon metabolism pathways and neural pathways are the mainly affected pathways by folate. Folate can increase mRNA mA modification through carbon metabolic pathway in human cells, especially in neural cells. We also show that folate treatment can significantly increase the expression of mA-related proteins (METTL3, METTL14) and neural mRNA mA methylation levels in mice brain. Moreover, we find that folate-producing Lactobacillus plantarum can increase host mRNA mA modification after colonization. In conclusion, we demonstrate that folate participates in mRNA mA modification through carbon metabolic pathway in both Drosophila and mammals, and our results suggest that folate has a significant effect on neural-related genes and pathways.