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Nutritional vitamin B12 regulates RAS/MAPK-mediated cell fate decisions through one-carbon metabolism

Author

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  • Ana Cristina Laranjeira

    (University of Zurich)

  • Simon Berger

    (University of Zurich
    ETH Zurich)

  • Tea Kohlbrenner

    (University of Zurich)

  • Nadja R. Greter

    (University of Zurich)

  • Alex Hajnal

    (University of Zurich)

Abstract

Vitamin B12 is an essential nutritional co-factor for the folate and methionine cycles, which together constitute one-carbon metabolism. Here, we show that dietary uptake of vitamin B12 modulates cell fate decisions controlled by the conserved RAS/MAPK signaling pathway in C. elegans. A bacterial diet rich in vitamin B12 increases vulval induction, germ cell apoptosis and oocyte differentiation. These effects are mediated by different one-carbon metabolites in a tissue-specific manner. Vitamin B12 enhances via the choline/phosphatidylcholine metabolism vulval induction by down-regulating fat biosynthesis genes and increasing H3K4 tri-methylation, which results in increased expression of RAS/MAPK target genes. Furthermore, the nucleoside metabolism and H3K4 tri-methylation positively regulate germ cell apoptosis and oocyte production. Using mammalian cells carrying different activated KRAS and BRAF alleles, we show that the effects of methionine on RAS/MAPK-regulated phenotype are conserved in mammals. Our findings suggest that the vitamin B12-dependent one-carbon metabolism is a limiting factor for diverse RAS/MAPK-induced cellular responses.

Suggested Citation

  • Ana Cristina Laranjeira & Simon Berger & Tea Kohlbrenner & Nadja R. Greter & Alex Hajnal, 2024. "Nutritional vitamin B12 regulates RAS/MAPK-mediated cell fate decisions through one-carbon metabolism," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52556-3
    DOI: 10.1038/s41467-024-52556-3
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    References listed on IDEAS

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    1. Eric L. Greer & Travis J. Maures & Anna G. Hauswirth & Erin M. Green & Dena S. Leeman & Géraldine S. Maro & Shuo Han & Max R. Banko & Or Gozani & Anne Brunet, 2010. "Members of the H3K4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans," Nature, Nature, vol. 466(7304), pages 383-387, July.
    2. Ziwei Dai & Samantha J. Mentch & Xia Gao & Sailendra N. Nichenametla & Jason W. Locasale, 2018. "Methionine metabolism influences genomic architecture and gene expression through H3K4me3 peak width," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    3. Qin-Li Wan & Xiao Meng & Chongyang Wang & Wenyu Dai & Zhenhuan Luo & Zhinan Yin & Zhenyu Ju & Xiaodie Fu & Jing Yang & Qunshan Ye & Zhan-Hui Zhang & Qinghua Zhou, 2022. "Histone H3K4me3 modification is a transgenerational epigenetic signal for lipid metabolism in Caenorhabditis elegans," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
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