Vitamin B12 Deficiency Dysregulates m6A mRNA Methylation of Genes Involved in Neurological Functions.

Scope Vitamin B12 deficiency presents various neurological manifestations, such as cognitive dysfunction, mental retardation, or memory impairment. However, the involved molecular mechanisms remain to date unclear. Vitamin B12 is essential for synthesizing S-adenosyl methionine (SAM), the methyl group donor used for almost all transmethylation reactions. Here, we investigated the m6A methylation of mRNAs and their related gene expression in models of vitamin B12 deficiency. Methods and results We studied two cellular models deficient in vitamin B12 and hippocampi of mice knock-out for the CD320 receptor. The decrease in SAM levels resulting from vitamin B12 deficiency was associated with m6 A reduced levels in mRNAs. This was also potentially mediated by the overexpression of the eraser FTO. We further investigated mRNA methylation of some genes involved in neurological functions targeted by the m6A reader YTH proteins. We notably observed a m6A hypermethylation of Prkca mRNA and a consistently increased expression of PKCα, a kinase involved in brain development and neuroplasticity, in the two cellular models. Conclusion Our data show that m6A methylation in mRNA could be one of the contributing mechanisms that underlie the neurological manifestations produced by vitamin B12 deficiency. This article is protected by copyright. All rights reserved.