Trm9-catalyzed tRNA modifications link translation to the DNA damage response
Trm9-catalyzed tRNA modifications link translation to the DNA damage response
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DOI：
10.1016/j.molcel.2007.09.021
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发表时间：
2007-12-14
期刊：
影响因子：
16
通讯作者：
Begley, Thomas J.
中科院分区：
文献类型：
--
作者：
Begley, Ulrike;Dyavaiah, Madhu;Begley, Thomas J.
转录和翻译后信号是促进对DNA损伤有效反应的已知机制。我们已经鉴定出酿酒酵母tRNA甲基转移酶9 （Trm9）是一种通过翻译增强DNA损伤反应蛋白来防止细胞死亡的酶。Trm9甲基化tRNA（ARG((U)在CU)）和tRNA（GLU((U)在UC)）的尿嘧啶摆动碱。我们使用计算和分子方法预测Trm9增强了一些被特定精氨酸和谷氨酸结肠过度代表的转录本的翻译。我们发现翻译延伸因子3 （YEF3）和核糖核苷酸还原酶（RNR1和RNR3）大亚基被特定的精氨酸和谷氨酸密码子过度代表，我们证明Trm9显著提高YEF3、RNR1和RNR3蛋白水平。此外，我们还鉴定了425个基因，其中包括YEF3、RNR1和RNR3，它们具有与Trm9相关的独特密码子使用模式。我们提出trm9特异性tRNA修饰增强密码子特异性翻译延伸并促进关键损伤反应蛋白水平的增加。
Transcriptional and posttranslational signals are known mechanisms that promote efficient responses to DNA damage. We have identified Saccharomyces cerevisiae tRNA methyltransferase 9 (Trm9) as an enzyme that prevents cell death via translational enhancement of DNA damage response proteins. Trm9 methylates the uridine wobble base of tRNA (ARG((U) under bar CU)) and tRNA(GLU((U) under bar UC)). We used computational and molecular approaches to predict that Trm9 enhances the translation of some transcripts overrepresented with specific arginine and glutamic acid coclons. We found that translation elongation factor 3 (YEF3) and the ribonucleotide reductase (RNR1 and RNR3) large subunits are overrepresented with specific arginine and glutamic acid codons, and we demonstrated that Trm9 significantly enhances Yef3, Rnr1, and Rnr3 protein levels. Additionally, we identified 425 genes, which included YEF3, RNR1, and RNR3, with a unique codon usage pattern linked to Trm9. We propose that Trm9-specific tRNA modifications enhance codon-specific translation elongation and promote increased levels of key damage response proteins.