A tRNA modification balances carbon and nitrogen metabolism by regulating phosphate homeostasis
- Institute for Stem Cell Biology and Regenerative Medicine (inStem), India
- Rutgers University, United States
Abstract
Cells must appropriately sense and integrate multiple metabolic resources to commit to proliferation. Here, we report that S. cerevisiae cells regulate carbon and nitrogen metabolic homeostasis through tRNA U34-thiolation. Despite amino acid sufficiency, tRNA-thiolation deficient cells appear amino acid starved. In these cells, carbon flux towards nucleotide synthesis decreases, and trehalose synthesis increases, resulting in a starvation-like metabolic signature. Thiolation mutants have only minor translation defects. However, in these cells phosphate homeostasis genes are strongly down-regulated, resulting in an effectively phosphate-limited state. Reduced phosphate enforces a metabolic switch, where glucose-6-phosphate is routed towards storage carbohydrates. Notably, trehalose synthesis, which releases phosphate and thereby restores phosphate availability, is central to this metabolic rewiring. Thus, cells use thiolated tRNAs to perceive amino acid sufficiency, balance carbon and amino acid metabolic flux and grow optimally, by controlling phosphate availability. These results further biochemically explain how phosphate availability determines a switch to a 'starvation-state'.
Data availability
Sequencing (transcript and ribosome footprint) data have been deposited in GEO under accession codes GSE124428, and are fully open.
Article and author information
Author details
Funding
Wellcome Trust - DBT India Alliance (IA/I/14/2/501523)
- Sunil Laxman
National Institutes of Health (GM124976)
- Premal Shah
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Gupta 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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A tRNA modification balances carbon and nitrogen metabolism by regulating phosphate homeostasis
eLife 8:e44795.
https://doi.org/10.7554/eLife.44795
