A tRNA modification balances carbon and nitrogen metabolism by regulating phosphate homeostasis.
|Title||A tRNA modification balances carbon and nitrogen metabolism by regulating phosphate homeostasis.|
|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Gupta R, Walvekar A, Liang S, Rashida Z, Shah P, Laxman S|
|Date Published||2019 Jul 01|
Cells must appropriately sense and integrate multiple metabolic resources to commit to proliferation. Here, we report that cells regulate carbon and nitrogen metabolic homeostasis through tRNA U-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'.
|Grant List||R35 GM124976 / GM / NIGMS NIH HHS / United States |
IA/I/14/2/501523 / / Wellcome Trust - DBT India Alliance /
GM124976 / / National Institutes of Health /