Work

A tRNA modification balances carbon and nitrogen metabolism by regulating phosphate homeostasis

Year: 2019

Type: article

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’.

Source: eLife

DOI: 10.7554/elife.44795

Authors: Ritu Gupta, Adhish S Walvekar, Shun Liang, Zeenat Rashida, Premal Shah, Sunil Laxman

Institutions: Institute for Stem Cell Biology and Regenerative Medicine, Rutgers, The State University of New Jersey, Manipal Academy of Higher Education

Language: English

Topic: RNA and protein synthesis mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $2,500