Translational control of one-carbon metabolism underpins ribosomal protein phenotypes in cell division and longevity
- Texas A&M University, United States
- Buck Institute for Research on Aging, United States
- University of Washington, United States
- Buck Institute For Research On Aging, United States
- 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.
Article and author information
Author details
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
- Jeff Smith, University of Virginia, United States
Version history
- Received: October 29, 2019
- Accepted: May 20, 2020
- Accepted Manuscript published: May 20, 2020 (version 1)
- 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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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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