翻译(生物学)
蛋白质生物合成
细胞生物学
生物
下调和上调
转移RNA
T细胞
细胞
核糖核酸
信使核糖核酸
分子生物学
基因
遗传学
免疫学
免疫系统
作者
Yongbo Liu,Jing Zhou,Xiaoyü Li,Xiaoting Zhang,Jintong Shi,Xuefei Wang,Hao Li,Song Miao,Huifang Chen,Xiaoxiao He,Liting Dong,Gap Ryol Lee,Junke Zheng,Ru-Juan Liu,Bing Su,Youqiong Ye,Richard A. Flavell,Chengqi Yi,Yuzhang Wu,Hua Bing Li
出处
期刊:Nature Immunology
[Springer Nature]
日期:2022-09-22
卷期号:23 (10): 1433-1444
被引量:38
标识
DOI:10.1038/s41590-022-01301-3
摘要
Naive T cells undergo radical changes during the transition from dormant to hyperactive states upon activation, which necessitates de novo protein production via transcription and translation. However, the mechanism whereby T cells globally promote translation remains largely unknown. Here, we show that on exit from quiescence, T cells upregulate transfer RNA (tRNA) m1A58 'writer' proteins TRMT61A and TRMT6, which confer m1A58 RNA modification on a specific subset of early expressed tRNAs. These m1A-modified early tRNAs enhance translation efficiency, enabling rapid and necessary synthesis of MYC and of a specific group of key functional proteins. The MYC protein then guides the exit of naive T cells from a quiescent state into a proliferative state and promotes rapid T cell expansion after activation. Conditional deletion of the Trmt61a gene in mouse CD4+ T cells causes MYC protein deficiency and cell cycle arrest, disrupts T cell expansion upon cognate antigen stimulation and alleviates colitis in a mouse adoptive transfer colitis model. Our study elucidates for the first time, to our knowledge, the in vivo physiological roles of tRNA-m1A58 modification in T cell-mediated pathogenesis and reveals a new mechanism of tRNA-m1A58-controlled T cell homeostasis and signal-dependent translational control of specific key proteins.
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