论文标题：Global analysis of tRNA and translation factor expression reveals a dynamic landscape of translational regulation in human cancers

期刊：

作者：Zhao Zhang, Youqiong Ye, Jing Gong, Hang Ruan, Chun-Jie Liu, Yu Xiang, Chunyan Cai, An-Yuan Guo, Jiqiang Ling, Lixia Diao, John N. Weinstein, Leng Han

发表时间：2018/12/21

数字识别码： 10.1038/s42003-018-0239-8

原文链接：

蛋白质翻译系统包括转运RNA（tRNA）和相关的几类酶，它在细胞增殖调控中起到了重要作用。而翻译调节异常则会引起癌症的发生。然而，在癌症中翻译系统到底发生了怎样的变化，目前我们了解得还不甚清晰。

来自德克萨斯大学的Leng Han团队近期在 Communications Biology发表的研究Global analysis of tRNA and translation factor expression reveals a dynamic landscape of translational regulation in human cancers中对于参与了翻译调控的tRNA和三类酶进行了全局分析，他们的团队分析了来自肿瘤基因组计划数据库（The Cancer Genome Atlas）中约一万名癌症患者，涵盖31种癌症类型的数据。

通过分析基因层面、密码子层面和氨基酸层面的tRNA表达水平，作者发现了tRNA表达的不均衡变化，这一现象很可能是由于解码不同密码子的tRNA分布不均导致的。研究发现，如果过表达识别密码子的tRNA具有较低的观察数-预期数比率，或许能够克服肿瘤发生过程中的翻译瓶颈。研究还观察到了tRNA修饰酶、氨酰tRNA合成酶、翻译因子的整体过表达和扩增。这些现象可能与tRNA过表达存在协同作用，在多种类型的癌症中共同激活翻译系统。

摘要：The protein translational system, including transfer RNAs (tRNAs) and several categories of enzymes, plays a key role in regulating cell proliferation. Translation dysregulation also contributes to cancer development, though relatively little is known about the changes that occur to the translational system in cancer. Here, we present global analyses of tRNAs and three categories of enzymes involved in translational regulation in ~10,000 cancer patients across 31 cancer types from The Cancer Genome Atlas. By analyzing the expression levels of tRNAs at the gene, codon, and amino acid levels, we identified unequal alterations in tRNA expression, likely due to the uneven distribution of tRNAs decoding different codons. We find that overexpression of tRNAs recognizing codons with a low observed-over-expected ratio may overcome the translational bottleneck in tumorigenesis. We further observed overall overexpression and amplification of tRNA modification enzymes, aminoacyl-tRNA synthetases, and translation factors, which may play synergistic roles with overexpression of tRNAs to activate the translational systems across multiple cancer types.

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