A tRNA modification balances carbon and nitrogen metabolism by regulating phosphate homeostasis.
Elife
; 82019 07 01.
Article
em En
| MEDLINE
| ID: mdl-31259691
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'.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfatos
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Saccharomyces cerevisiae
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Compostos de Sulfidrila
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RNA de Transferência
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Carbono
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Processamento Pós-Transcricional do RNA
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Nitrogênio
Idioma:
En
Revista:
Elife
Ano de publicação:
2019
Tipo de documento:
Article