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

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.

Automated summary

ROS in activated T cells triggers an oxidative stress response leading to translation repression, which is countered by SLFN2 binding tRNAs. SLFN2 deficiency results in tRNA fragment accumulation, inhibiting translation and promoting stress-granule formation.