C. elegans methionine/S-adenosylmethionine cycle activity is sensed and adjusted by a nuclear hormone receptor

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Abstract

Vitamin B12 is an essential micronutrient that functions in two metabolic pathways: the canonical propionate breakdown pathway and the methionine/S-adenosylmethionine (Met/SAM) cycle. In Caenorhabditis elegans, low vitamin B12, or genetic perturbation of the canonical propionate breakdown pathway results in propionate accumulation and the transcriptional activation of a propionate shunt pathway. This propionate-dependent mechanism requires nhr-10 and is referred to as 'B12-mechanism-I'. Here, we report that vitamin B12 represses the expression of Met/SAM cycle genes by a propionate-independent mechanism we refer to as 'B12-mechanism-II'. This mechanism is activated by perturbations in the Met/SAM cycle, genetically or due to low dietary vitamin B12. B12-mechanism-II requires nhr-114 to activate Met/SAM cycle gene expression, the vitamin B12 transporter, pmp-5, and adjust influx and efflux of the cycle by activating msra-1 and repressing cbs-1, respectively. Taken together, Met/SAM cycle activity is sensed and transcriptionally adjusted to be in a tight metabolic regime.

Data availability

Sequencing data have been deposited in GEO under accession codes GSE123507 and GSE151848

The following data sets were generated

1. Giese G
(2020) C. elegans methionine/S-adenosylmethionine cycle activity is sensed and adjusted by a nuclear hormone receptor
NCBI Gene Expression Omnibus, GSE151848.

http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE151848

The following previously published data sets were used

1. Bulcha JT
2. Walhout AJ
(2019) A persistence detector for metabolic network rewiring in an animal
NCBI Gene Expression Omnibus, GSE123507.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE123507

Article and author information

Author details

Gabrielle E Giese

Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States

Competing interests
The authors declare that no competing interests exist.
Melissa D Walker

Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States

Competing interests
The authors declare that no competing interests exist.
Olga Ponomarova

Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States

Competing interests
The authors declare that no competing interests exist.
Hefei Zhang

Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States

Competing interests
The authors declare that no competing interests exist.
Xuhang Li

Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States

Competing interests
The authors declare that no competing interests exist.
Gregory Minevich

Department of Biochemistry and Molecular Biophysics, Columbia University, New York City, United States

Competing interests
The authors declare that no competing interests exist.
Albertha JM Walhout

Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States

For correspondence
marian.walhout@umassmed.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-5587-3608

Funding

National Institutes of Health (DK068429)

Albertha JM Walhout

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.