Eri1 regulates microRNA homeostasis and mouse lymphocyte development and antiviral function.
Blood, 2012/7/05;120(1):130-42.
Thomas MF[1], Abdul-Wajid S, Panduro M, Babiarz JE, Rajaram M, Woodruff P, Lanier LL, Heissmeyer V, Ansel KM
Affiliations
PMID: 22613798DOI: 10.1182/blood-2011-11-394072
Impact factor: 25.476
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.
MeSH terms
Adoptive Transfer; Animals; Bone Marrow Cells; CD4-Positive T-Lymphocytes; Cells, Cultured; Cytomegalovirus Infections; Exonucleases; Exoribonucleases; Homeostasis; Killer Cells, Natural; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Mutant Strains; MicroRNAs; NK Cell Lectin-Like Receptor Subfamily A
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