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

INTRODUCTION

Vitamin B deficiency presents various neurological manifestations, such as cognitive dysfunction, mental retardation, or memory impairment. However, the involved molecular mechanisms remain to date unclear. Vitamin B is essential for synthesizing S-adenosyl methionine (SAM), the methyl group donor used for almost all transmethylation reactions. Here, we investigate the m6A methylation of mRNAs and their related gene expression in models of vitamin B deficiency.

METHODS AND RESULTS

This study observes two cellular models deficient in vitamin B and hippocampi of mice knock-out for the CD320 receptor. The decrease in SAM levels resulting from vitamin B deficiency is associated with m A reduced levels in mRNAs. This is also potentially mediated by the overexpression of the eraser FTO. We further investigate mRNA methylation of some genes involved in neurological functions targeted by the m6A reader YTH proteins. We notably observe 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 B deficiency.