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 language | English (US) |
|---|---|
| Journal | Cell |
| Volume | 154 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jul 18 2013 |
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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 journal › Article
}
TY - JOUR
T1 - XSulfur amino acids regulate translational capacity and metabolic homeostasis through modulation of tRNA thiolation
AU - Laxman, Sunil
AU - Sutter, Benjamin M.
AU - Wu, Xi
AU - Kumar, Sujai
AU - Guo, Xiaofeng
AU - Trudgian, David C.
AU - Mirzaei, Hamid
AU - Tu, Benjamin P.
PY - 2013/7/18
Y1 - 2013/7/18
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cell.2013.06.043
DO - 10.1016/j.cell.2013.06.043
M3 - Article
C2 - 23870129
AN - SCOPUS:84880536607
VL - 154
JO - Cell
JF - Cell
SN - 0092-8674
IS - 2
ER -