title: Sulfur amino acids regulate translational capacity and metabolic homeostasis through modulation of tRNA thiolation.
abstract: Protein translation is an energetically demanding process that must be regulated in response to changes in nutrient availability. Herein, we report that intracellular methionine and cysteine availability directly controls the thiolation status of wobble-uridine (U34) nucleotides present on lysine, glutamine, or glutamate tRNAs to regulate cellular translational capacity and metabolic homeostasis. tRNA thiolation is important for growth under nutritionally challenging environments and required for efficient translation of genes enriched in lysine, glutamine, and glutamate codons, which are enriched in proteins important for translation and growth-specific processes. tRNA thiolation is downregulated during sulfur starvation in order to decrease sulfur consumption and growth, and its absence leads to a compensatory increase in enzymes involved in methionine, cysteine, and lysine biosynthesis. Thus, tRNA thiolation enables cells to modulate translational capacity according to the availability of sulfur amino acids, establishing a functional significance for this conserved tRNA nucleotide modification in cell growth control.
authors.affiliation: Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9038, USA.
authors.forename: Sunil
authors.initials: S
authors.lastname: Laxman
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Sutter
authors.forename: Xi
authors.initials: X
authors.lastname: Wu
authors.forename: Sujai
authors.initials: S
authors.lastname: Kumar
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Guo
authors.forename: David C
authors.initials: DC
authors.lastname: Trudgian
authors.forename: Hamid
authors.initials: H
authors.lastname: Mirzaei
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Tu
mesh_terms: D000603:Amino Acids, Sulfur / Q000378:metabolism*; D015536:Down-Regulation; D014176:Protein Biosynthesis; D012343:RNA, Transfer / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014529:Uridine / Q000378:metabolism*
chemical_list: D000603:Amino Acids, Sulfur; D029701:Saccharomyces cerevisiae Proteins; C406283:UBA4 protein, S cerevisiae; D012343:RNA, Transfer; D014529:Uridine