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.
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.
Paralog-specific phenotypes of ribosomal protein mutants identify translational control mechanisms in the cell cycle and replicative longevityNCBI Gene Expression Omnibus, GEO GSE135336.
- Rodolfo Aramayo
- Brian K Kennedy
- Michael Polymenis
- Birgit Schilling
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Jeff Smith, University of Virginia, United States
© 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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