Nature Immunology
22 September 2022
tRNA-m1A modification promotes T cell expansion via efficient MYC protein synthesis
Yongbo Liu1,2,†, Jing Zhou1,2,3,†, Xiaoyu Li4,†, Xiaoting Zhang5,†, Jintong Shi1,†, Xuefei Wang1,2, Hao Li6, Shan Miao1,2, Huifang Chen1,7, Xiaoxiao He8, Liting Dong5,9, Gap Ryol Lee10, Junke Zheng8, Ru-Juan Liu6, Bing Su1,2, Youqiong Ye1, Richard A. Flavell3,11✉, Chengqi Yi5,9,12✉, Yuzhang Wu7✉ & Hua-Bing Li1,2,7,13✉
1 Shanghai Institute of Immunology, State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai, China
2 Shanghai Jiao Tong University School of Medicine-Yale Institute for Immune Metabolism, Shanghai Jiao Tong University School of Medicine, Shanghai, China
3 Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA
4 Department of Biochemistry and Department of Gastroenterology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
5 State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China
6 School of Life Science and Technology, ShanghaiTech University, Shanghai, China
7 Chongqing International Institute for Immunology, Chongqing, China
8 Hongqiao International Institute of Medicine, Shanghai Tongren Hospital, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China
9 Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China
10 Department of Life Science, Sogang University, Seoul, Republic of Korea
11 Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, USA
12 Department of Chemical Biology and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing, China
13 Department of Geriatrics, Medical Center on Aging of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
† These authors contributed equally.
10.1038/s41590-022-01301-3
Naive T cells are quiescent but undergo dynamic changes after antigenic activation. Flavell and colleagues show that upregulation of the tRNA methyltransferase proteins TRMT61A and TRMT6 and N1-methyladenosine modification of tRNAs contribute to accelerated mRNA translation efficiency, in particular synthesis of MYC protein, and are required for rapid T cell proliferation.
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