The role of vitamin B12 in the regulation of gene expression and cellular metabolome during animal development

Hencel, Katarzyna Maria (2025) The role of vitamin B12 in the regulation of gene expression and cellular metabolome during animal development. Doctoral thesis, University of East Anglia.

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Abstract

One carbon metabolism is a network of metabolic processes essential for synthesising nucleotides, maintaining cellular redox balance, and providing the cell with methyl groups. It comprises three pathways: folate and methionine cycles and the transsulfuration pathway. Methionine and folate cycles are linked at the step of homocysteine conversion into methionine, catalysed by methionine synthase. Methionine is converted into S-adenosylmethionine (SAM), a major methyl donor in the cell, which provides methyl groups essential for signalling and nucleic acid modifications.

Many intermediates in one carbon metabolism are derived from the diet, and the vast evidence shows that diet and nutritional deficiencies, including vitamin B12, can directly regulate the functionality of one carbon metabolism. Vitamin B12 is a cofactor in one-carbon metabolism and is essential for the conversion of homocysteine into methionine. Its deficiency has been linked to developmental retardation, infertility, and neurological problems. On a molecular level, vitamin B12 deficiency can lead to a reduction of the cellular methyl pool. Methyl groups deposited on nucleic acids are crucial for gene expression regulation and downstream processes, including transcription, translation, and splicing. The association between the nutritional regulation of cellular methylome has been widely studied, with much evidence showing its regulation in DNA and histone protein modifications. However, much less is known about RNA modifications.

C. elegans is a free-living soil nematode widely used in genetic and metabolic research. During this project, I explored a novel vitamin B12-deficient dietary system to use in C. elegans to study the effect of the deficiency on gene expression regulation, including nucleic acid processes and cellular metabolome changes, to uncover the molecular mechanisms behind the physiological consequences of the deficiency.

In this study, I show that vitamin B12 deficiency leads to the upregulation of immunity and oxidative stress responses and differential expression of RNA methyltransferases, which does not lead to hypomethylation of a known splicing regulator. Additionally, genetic manipulation of C. elegans diet, Comamonas aquatica DA1877, known to accelerate C. elegans development, previously attributed to high quantities of vitamin B12, revealed that vitamin B12 is not the only metabolite responsible for C. elegans developmental acceleration.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	Kitty Laine
Date Deposited:	11 Jun 2025 11:09
Last Modified:	11 Jun 2025 11:09
URI:	https://ueaeprints.uea.ac.uk/id/eprint/99454
DOI:

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