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

Tao Yue, Xiaoming Zhan, Duanwu Zhang, Ruchi Jain, Kuan Wen Wang, Jin Huk Choi, Takuma Misawa, Lijing Su, Jiexia Quan, Sara Hildebrand, Darui Xu, Xiaohong Li, Emre Turer, Lei Sun, Eva Marie Y. Moresco, Bruce Beutler

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

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 b (IL-2Rb) and IL-2Rg 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.

Original languageEnglish (US)
Article numbereaba4220
JournalScience
Volume372
Issue number6543
DOIs
StatePublished - May 14 2021

ASJC Scopus subject areas

  • General

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