Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9038, USA.
Cell. 2013 Jul 18;154(2):416-29. doi: 10.1016/j.cell.2013.06.043.
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.
蛋白质翻译是一个能量需求很高的过程，必须根据营养物质可用性的变化进行调节。在此，我们报告说，细胞内蛋氨酸和半胱氨酸的可用性直接控制赖氨酸、谷氨酰胺或谷氨酸 tRNA 上的摆动尿嘧啶（U34）核苷酸的巯基化状态，以调节细胞的翻译能力和代谢平衡。tRNA 巯基化对于在营养挑战环境下的生长很重要，并且对于富含赖氨酸、谷氨酰胺和谷氨酸密码子的基因的有效翻译是必需的，这些基因富含对翻译和生长特定过程很重要的蛋白质。硫饥饿时，tRNA 巯基化会下调，以减少硫的消耗和生长，其缺失会导致参与蛋氨酸、半胱氨酸和赖氨酸生物合成的酶代偿性增加。因此，tRNA 巯基化使细胞能够根据硫氨基酸的可用性来调节翻译能力，为这种保守的 tRNA 核苷酸修饰在细胞生长控制中的功能意义奠定了基础。
