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.
N1 - Funding Information:
We thank Uttam Tambar for suggestions during the synthesis of APM; Randal Halfmann, Paul Dutchak, and members of the Tu Lab for extensive discussions and critical input. This work was supported by the UTSW Endowed Scholars Program, the Welch Foundation (I-1797), award R01GM094314 from NIGMS, the Burroughs Wellcome Fund, the David and Lucile Packard Foundation, and the Damon Runyon Cancer Research Foundation. B.P.T. is a consultant and shareholder of Peloton Therapeutics.
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
SN - 0092-8674
VL - 154
SP - 416
JO - Cell
JF - Cell
IS - 2
ER -