XSulfur amino acids regulate translational capacity and metabolic homeostasis through modulation of tRNA thiolation

Sunil Laxman, Benjamin M. Sutter, Xi Wu, Sujai Kumar, Xiaofeng Guo, David C. Trudgian, Hamid Mirzaei, Benjamin P. Tu

Research output: Contribution to journalArticle

90 Citations (Scopus)

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.

Original languageEnglish (US)
JournalCell
Volume154
Issue number2
DOIs
StatePublished - Jul 18 2013

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Transfer RNA
Homeostasis
Modulation
Amino Acids
Lysine
Availability
Protein Biosynthesis
Growth
Glutamine
Sulfur
Methionine
Cysteine
Glutamic Acid
Uracil Nucleotides
Sulfur Amino Acids
Biosynthesis
Cell growth
Starvation
Codon
Nutrients

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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XSulfur amino acids regulate translational capacity and metabolic homeostasis through modulation of tRNA thiolation. / Laxman, Sunil; Sutter, Benjamin M.; Wu, Xi; Kumar, Sujai; Guo, Xiaofeng; Trudgian, David C.; Mirzaei, Hamid; Tu, Benjamin P.

In: Cell, Vol. 154, No. 2, 18.07.2013.

Research output: Contribution to journalArticle

Laxman, Sunil ; Sutter, Benjamin M. ; Wu, Xi ; Kumar, Sujai ; Guo, Xiaofeng ; Trudgian, David C. ; Mirzaei, Hamid ; Tu, Benjamin P. / XSulfur amino acids regulate translational capacity and metabolic homeostasis through modulation of tRNA thiolation. In: Cell. 2013 ; Vol. 154, No. 2.
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