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

  1. Gabrielle E Giese
  2. Melissa D Walker
  3. Olga Ponomarova
  4. Hefei Zhang
  5. Xuhang Li
  6. Gregory Minevich
  7. Albertha JM Walhout  Is a corresponding author
  1. University of Massachusetts Medical School, United States
  2. Columbia University, United States

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
The following previously published data sets were used

Article and author information

Author details

  1. 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.
  2. 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.
  3. Olga Ponomarova

    Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Hefei Zhang

    Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Xuhang Li

    Program in Systems Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. 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.
  7. 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.
    ORCID icon "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.

Reviewing Editor

  1. Oliver Hobert, Howard Hughes Medical Institute, Columbia University, United States

Publication history

  1. Received: June 22, 2020
  2. Accepted: October 2, 2020
  3. Accepted Manuscript published: October 5, 2020 (version 1)
  4. Version of Record published: October 15, 2020 (version 2)

Copyright

© 2020, Giese et al.

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.

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  1. Gabrielle E Giese
  2. Melissa D Walker
  3. Olga Ponomarova
  4. Hefei Zhang
  5. Xuhang Li
  6. Gregory Minevich
  7. Albertha JM Walhout
(2020)
C. elegans methionine/S-adenosylmethionine cycle activity is sensed and adjusted by a nuclear hormone receptor
eLife 9:e60259.
https://doi.org/10.7554/eLife.60259
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