Translational control of one-carbon metabolism underpins ribosomal protein phenotypes in cell division and longevity

  1. Nairita Maitra
  2. Chong He
  3. Heidi M Blank
  4. Mitsuhiro Tsuchiya
  5. Birgit Schilling
  6. Matt Kaeberlein
  7. Rodolfo Aramayo
  8. Brian K Kennedy  Is a corresponding author
  9. Michael Polymenis  Is a corresponding author
  1. Texas A&M University, United States
  2. Buck Institute for Research on Aging, United States
  3. University of Washington, United States
  4. Buck Institute For Research On Aging, United States
  5. National University of Singapore, Singapore

Abstract

A long-standing problem is how cells that lack one of the highly similar ribosomal proteins (RPs) often display distinct phenotypes. Yeast and other organisms live longer when they lack specific ribosomal proteins, especially of the large 60S subunit of the ribosome. However, longevity is neither associated with the generation time of RP deletion mutants nor with bulk inhibition of protein synthesis. Here, we queried actively dividing RP mutants through the cell cycle. Our data link transcriptional, translational, and metabolic changes to phenotypes associated with the loss of paralogous RPs. We uncovered translational control of transcripts encoding enzymes of methionine and serine metabolism, which are part of one-carbon (1C) pathways. Cells lacking Rpl22Ap, which are long-lived, have lower levels of metabolites associated with 1C metabolism. Loss of 1C enzymes increased the longevity of wild type cells. 1C pathways exist in all organisms and targeting the relevant enzymes could represent longevity interventions.

Data availability

Sequencing data have been deposited in GEO under accession code GSE135336. All data generated or analysed during this study are included in the manuscript and supporting files.

The following data sets were generated

Article and author information

Author details

  1. Nairita Maitra

    Biochemistry and Biophysics, Texas A&M University, College Station, United States
    Competing interests
    No competing interests declared.
  2. Chong He

    Buck Institute for Research on Aging, Novato, United States
    Competing interests
    No competing interests declared.
  3. Heidi M Blank

    Biochemistry and Biophysics, Texas A&M University, College Station, United States
    Competing interests
    No competing interests declared.
  4. Mitsuhiro Tsuchiya

    Pathology, University of Washington, Seattle, United States
    Competing interests
    No competing interests declared.
  5. Birgit Schilling

    Buck Institute For Research On Aging, Novato, United States
    Competing interests
    No competing interests declared.
  6. Matt Kaeberlein

    Department of Pathology, University of Washington, Seattle, United States
    Competing interests
    Matt Kaeberlein, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1311-3421
  7. Rodolfo Aramayo

    Biology, Texas A&M University, College Station, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9702-6204
  8. Brian K Kennedy

    National University of Singapore, Singapore, Singapore
    For correspondence
    bkennedy@nus.edu.sg
    Competing interests
    No competing interests declared.
  9. Michael Polymenis

    Biochemistry and Biophysics, Texas A&M University, College Station, United States
    For correspondence
    polymenis@tamu.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1507-0936

Funding

National Institutes of Health (GM123139)

  • Rodolfo Aramayo
  • Brian K Kennedy
  • Michael Polymenis

National Center for Research Resources (1S10 OD016281)

  • Birgit Schilling

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

Reviewing Editor

  1. Jeff Smith, University of Virginia, United States

Publication history

  1. Received: October 29, 2019
  2. Accepted: May 20, 2020
  3. Accepted Manuscript published: May 20, 2020 (version 1)
  4. Version of Record published: June 1, 2020 (version 2)

Copyright

© 2020, Maitra 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. Nairita Maitra
  2. Chong He
  3. Heidi M Blank
  4. Mitsuhiro Tsuchiya
  5. Birgit Schilling
  6. Matt Kaeberlein
  7. Rodolfo Aramayo
  8. Brian K Kennedy
  9. Michael Polymenis
(2020)
Translational control of one-carbon metabolism underpins ribosomal protein phenotypes in cell division and longevity
eLife 9:e53127.
https://doi.org/10.7554/eLife.53127

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