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Eri1 regulates microRNA homeostasis and mouse lymphocyte development and antiviral function

  • Author(s): Thomas, MF
  • Abdul-Wajid, S
  • Panduro, M
  • Babiarz, JE
  • Rajaram, M
  • Woodruff, P
  • Lanier, LL
  • Heissmeyer, V
  • Ansel, KM
  • et al.
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 (BM) and a selective reduction in Ly49D and Ly49H activating receptors in the periphery. Eri1 was required for immune-mediated control of mouse CMV (MCMV) infection. Ly49H + NK cells deficient in Eri1 failed to expand efficiently during MCMV infection, and virus-specific responses were also diminished among Eri1 -/- T cells. 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 antiviral immunity. © 2012 by The American Society of Hematology.

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