Vitamin B12 Deficiency Dysregulates m6A mRNA Methylation of Genes Involved in Neurological Functions. Issue 17 (29th July 2021)

• Record Type: Journal Article
• Authors: Mosca, Pauline; Robert, Aurélie; Alberto, Jean‐Marc; Meyer, Marie; Kundu, Urbi; Hergalant, Sébastien; Umoret, Rémy; Coelho, David; Guéant, Jean‐Louis; Leheup, Bruno; Dreumont, Natacha
• Is Part Of: Molecular nutrition & food research. Volume 65:Issue 17(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-07-29
• Subjects: epitranscriptomics -- m6A -- methylation -- nutrient -- vitamin B12; Food -- Biotechnology -- Periodicals; Food -- Microbiology -- Periodicals; Nutrition -- Periodicals; Food -- Toxicology -- Periodicals; Nutrition -- Periodicals; Food Microbiology -- Periodicals; Food Technology -- Periodicals; Molecular Biology -- Periodicals; 664.0705
• DOI: 10.1002/mnfr.202100206
• Languages: English
• ISSNs: 1613-4125

Abstract

Abstract : Introduction: 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 investigate the m6A methylation of mRNAs and their related gene expression in models of vitamin B12 deficiency. Methods and Results: This study observes 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 is associated with m 6 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 B12 deficiency. Abstract : Vitamin B12 is essential for the synthesis of S‐adenosylmethionine (SAM), which is used for transmethylation reactions. This study observes that mRNAs presented with a dysregulated m6A status in cells deficient in vitamin B12, caused either by SAM decrease or FTO overexpression. Some are hypomethylated, whereas Prkca mRNA is hypermethylated, resulting in an increased level of the corresponding protein, a kinase involved in many neurological pathways.