Liu Anrui, Huo Zhengyi, Xu Zihe, Liu Sisi, Jiao Yuting, Li Rui, Lu Yi, Yang Meng, Huang Jia, Huang Chen, Wang Xiaoyun
Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
School of Life Sciences, South China Normal University, Guangzhou, China.
Commun Biol. 2025 Aug 4;8(1):1151. doi: 10.1038/s42003-025-08623-6.
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.
越来越多的证据表明，叶酸可通过DNA修饰来调节神经基因功能，而叶酸在神经RNA修饰中的调节作用仍 largely未知。在此我们表明，叶酸处理显著提高了果蝇mRNA mA水平。RNA甲基化分析表明，碳代谢途径和神经途径是叶酸主要影响的途径。叶酸可通过碳代谢途径在人类细胞尤其是神经细胞中增加mRNA mA修饰。我们还表明，叶酸处理可显著提高小鼠大脑中mA相关蛋白（METTL3、METTL14）的表达以及神经mRNA mA甲基化水平。此外，我们发现产叶酸的植物乳杆菌在定殖后可增加宿主mRNA mA修饰。总之，我们证明叶酸在果蝇和哺乳动物中均通过碳代谢途径参与mRNA mA修饰，并且我们的结果表明叶酸对神经相关基因和途径具有显著影响。
