Eri1 regulates microRNA homeostasis and mouse natural killer cell development and anti-viral function (115.9)

Abstract Natural killer (NK) cells play a critical role in early host defense to infected and transformed cells. Here we show that mice deficient in Eri1, a conserved 3’-to-5’ exoribonuclease that represses RNA interference, have a cell-intrinsic defect in NK cell development and maturation. Eri1-/- NK cells displayed delayed acquisition of Ly49 receptors in the bone marrow and a selective reduction in Ly49D and Ly49H activating receptors in the periphery. Furthermore, Ly49H+ NK cells deficient in Eri1 failed to expand efficiently during mouse cytomegalovirus (MCMV) infection. Consequently, Eri1 was required for immune-mediated control of MCMV. We identified miRNAs as the major endogenous small RNA target of Eri1 in mouse lymphocytes. Both NK and T cells deficient in Eri1 displayed a global, sequence-independent increase in miRNA abundance. Ectopic Eri1 expression rescued defective miRNA expression in mature Eri1-/- T cells. Thus mouse Eri1 regulates miRNA homeostasis in lymphocytes and is required for normal NK cell development and anti-viral immunity.