LAUSR

Protection of transfer RNAs from fragmentation avoids overstressing T cells When exposed to external antigens, T cells are rapidly activated to proliferate and differentiate. A genetic screen identified a mutation called elektra that causes immunodeficiency in mice through a single loss-of-function missense mutation in the Schlafen 2 (Slfn2) gene (1). Slfn2 mutation was associated with impaired T cell activation. However, whether Slfn2 regulates T cell function directly, and how, was unclear. On page 703 of this issue, Yue et al. (2) report that SLFN2 safeguards T cells from excessive stress during activation and thus facilitates the necessary up-regulation of protein translation. SLFN2 binds and shields transfer RNAs (tRNAs), essential adaptor molecules in translation of messenger RNAs (mRNAs), from stress-activated fragmentation. Without SLFN2, excessive tRNA fragmentation lowers global translation and specifically decreases the translation of key cytokine receptor proteins important for T cell activation. This study expands the role of tRNA fragmentation and implicates SLFN2 in preventing fragmentation to enable immune function.