title: Eri1 regulates microRNA homeostasis and mouse lymphocyte development and antiviral function.
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.
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Molly F
authors.initials: MF
authors.lastname: Thomas
authors.forename: Sarah
authors.initials: S
authors.lastname: Abdul-Wajid
authors.forename: Marisella
authors.initials: M
authors.lastname: Panduro
authors.forename: Joshua E
authors.initials: JE
authors.lastname: Babiarz
authors.forename: Misha
authors.initials: M
authors.lastname: Rajaram
authors.forename: Prescott
authors.initials: P
authors.lastname: Woodruff
authors.forename: Lewis L
authors.initials: LL
authors.lastname: Lanier
authors.forename: Vigo
authors.initials: V
authors.lastname: Heissmeyer
authors.forename: K Mark
authors.initials: KM
authors.lastname: Ansel
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000821:virology; D002478:Cells, Cultured; D003586:Cytomegalovirus Infections / Q000276:immunology*; D005092:Exonucleases / Q000235:genetics* / Q000276:immunology*; D005095:Exoribonucleases; D006706:Homeostasis / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008817:Mice, Mutant Strains; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D055650:NK Cell Lectin-Like Receptor Subfamily A / Q000276:immunology / Q000378:metabolism
chemical_list: C527092:Klra4 protein, mouse; C527096:Klra8 protein, mouse; D035683:MicroRNAs; D055650:NK Cell Lectin-Like Receptor Subfamily A; C507007:Eri1 protein, mouse; D005092:Exonucleases; D005095:Exoribonucleases