SLFN2 protection of tRNAs from stress-induced cleavage is essential for T cell-mediated immunity

被引：59

作者：

Yue, Tao ^{[1
]}

Zhan, Xiaoming ^{[1
]}

Zhang, Duanwu ^{[1
,3
,4
]}

Jain, Ruchi ^{[1
]}

Wang, Kuan-Wen ^{[1
]}

Choi, Jin Huk ^{[1
]}

Misawa, Takuma ^{[1
,5
]}

Su, Lijing ^{[1
]}

Quan, Jiexia ^{[1
]}

Hildebrand, Sara ^{[1
]}

Xu, Darui ^{[1
]}

Li, Xiaohong ^{[1
]}

Turer, Emre ^{[1
,2
]}

Sun, Lei ^{[1
,4
,6
]}

Moresco, Eva Marie Y. ^{[1
]}

Beutler, Bruce ^{[1
]}

机构：

[1] Univ Texas Southwestern Med Ctr, Ctr Genet Host Def, Dallas, TX 75390 USA

[2] Univ Texas Southwestern Med Ctr, Dept Internal Med, Div Gastroenterol, Dallas, TX 75390 USA

[3] Fudan Univ, Childrens Hosp, Shanghai 200032, Peoples R China

[4] Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China

[5] RIKEN, Lab Immune Cell Syst, Ctr Integrat Med Sci, Yokohama, Kanagawa 2300045, Japan

[6] Fudan Univ, Peoples Hosp Shanghai 5, Shanghai 201100, Peoples R China

来源：

SCIENCE | 2021年 / 372卷 / 6543期

基金：

美国国家卫生研究院;

关键词：

ANGIOGENIN; ACTIVATION; PROTEIN; GENE; GROWTH; DIFFERENTIATION; INTERLEUKIN-2; PROLIFERATION; RIBONUCLEASE; TRANSLATION;

D O I：

10.1126/science.aba4220

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Reactive oxygen species (ROS) increase in activated T cells because of metabolic activity induced to support T cell proliferation and differentiation. We show that these ROS trigger an oxidative stress response that leads to translation repression. This response is countered by Schlafen 2 (SLFN2), which directly binds transfer RNAs (tRNAs) to protect them from cleavage by the ribonuclease angiogenin. T cell-specific SLFN2 deficiency results in the accumulation of tRNA fragments, which inhibit translation and promote stress-granule formation. Interleukin-2 receptor beta (IL-2R beta) and IL-2R gamma fail to be translationally up-regulated after T cell receptor stimulation, rendering SLFN2-deficient T cells insensitive to interleukin-2's mitogenic effects. SLFN2 confers resistance against the ROS-mediated translation-inhibitory effects of oxidative stress normally induced by T cell activation, permitting the robust protein synthesis necessary for T cell expansion and immunity.

引用

页码：703 / +

页数：41

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