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

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 m6 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.

• Authors: Pauline Mosca, Aurélie Robert, Jean-Marc Alberto, Marie Meyer, Urbi Kundu, Sébastien Hergalant, Rémy Umoret, David Coelho, Jean-Louis Guéant, Bruno Leheup, Natacha Dreumont
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 65 Issue 17 Pg. e2100206 (09 2021) ISSN: 1613-4133 [Electronic] Germany
• PMID: 34291881 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 Wiley-VCH GmbH.

Chemical References

• RNA, Messenger
• Receptors, Cell Surface
• Recombinant Fusion Proteins
• Transcobalamins
• transcobalamin receptor
• S-Adenosylmethionine
• N-methyladenosine
• Prkca protein, mouse
• Protein Kinase C-alpha
• Adenosine

Topics

• Adenosine (analogs & derivatives, genetics)
• Animals
• Fibroblasts
• Gene Expression Regulation
• Methylation
• Mice, Knockout
• Protein Kinase C-alpha (genetics, metabolism)
• RNA, Messenger (metabolism)
• Receptors, Cell Surface (genetics)
• Recombinant Fusion Proteins (genetics, metabolism)
• S-Adenosylmethionine (metabolism)
• Transcobalamins (genetics, metabolism)
• Vitamin B 12 Deficiency (genetics, metabolism, physiopathology)
• Mice