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

Elife. 2019 Jul 1;8:e44795. doi: 10.7554/eLife.44795.

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'.

Keywords: S. cerevisiae; biochemistry; cell cycle; chemical biology; genetics; genomics; metabolism; methionine; phosphate; tRNA modification; trehalose.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbon / metabolism*
  • Gene Expression Regulation, Fungal
  • Homeostasis
  • Nitrogen / metabolism*
  • Phosphates / metabolism*
  • RNA Processing, Post-Transcriptional*
  • RNA, Transfer / metabolism*
  • Saccharomyces cerevisiae / metabolism*
  • Sulfhydryl Compounds / metabolism*

Substances

  • Phosphates
  • Sulfhydryl Compounds
  • Carbon
  • RNA, Transfer
  • Nitrogen

Associated data

  • GEO/GSE124428