转移RNA
生物
翻译(生物学)
翻译效率
甲基转移酶
基因敲除
核糖核酸
肺癌
表观遗传学
信使核糖核酸
癌症研究
甲基化
基因
平动调节
基因表达
蛋白质生物合成
真核翻译
作者
Jieyi Ma,Hui Han,Ying Huang,Chunlong Yang,Siyi Zheng,Tiancai Cai,Jiong Bi,Xiao-Hui Huang,Rui-Ming Liu,Libin Huang,Yifeng Luo,Wen Li,Shuibin Lin
标识
DOI:10.1016/j.ymthe.2021.08.005
摘要
Mis-regulated epigenetic modifications in RNAs are associated with human cancers. The transfer RNAs (tRNAs) are the most heavily modified RNA species in cells; however, little is known about the functions of tRNA modifications in cancers. In this study, we uncovered that the expression levels of tRNA N7-methylguanosine (m7G) methyltransferase complex components methyltransferase-like 1 (METTL1) and WD repeat domain 4 (WDR4) are significantly elevated in human lung cancer samples and negatively associated with patient prognosis. Impaired m7G tRNA modification upon METTL1/WDR4 depletion resulted in decreased cell proliferation, colony formation, cell invasion, and impaired tumorigenic capacities of lung cancer cells in vitro and in vivo. Moreover, gain-of-function and mutagenesis experiments revealed that METTL1 promoted lung cancer growth and invasion through regulation of m7G tRNA modifications. Profiling of tRNA methylation and mRNA translation revealed that highly translated mRNAs have higher frequencies of m7G tRNA-decoded codons, and knockdown of METTL1 resulted in decreased translation of mRNAs with higher frequencies of m7G tRNA codons, suggesting that tRNA modifications and codon usage play an essential function in mRNA translation regulation. Our data uncovered novel insights on mRNA translation regulation through tRNA modifications and the corresponding mRNA codon compositions in lung cancer, providing a new molecular basis underlying lung cancer progression.
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