title: Type I interferon controls propagation of long interspersed element-1.
abstract: Type I interferons (IFN) including IFNα and IFNβ are critical for the cellular defense against viruses. Here we report that increased levels of IFNβ were found in testes from mice deficient in MOV10L1, a germ cell-specific RNA helicase that plays a key role in limiting the propagation of retrotransposons including Long Interspersed Element-1 (LINE-1). Additional experiments revealed that activation of LINE-1 retrotransposons increases the expression of IFNβ and of IFN-stimulated genes. Conversely, pretreatment of cells with IFN suppressed the replication of LINE-1. Furthermore, the efficacy of LINE-1 replication was increased in isogenic cell lines harboring inactivating mutations in diverse elements of the IFN signaling pathway. Knockdown of the IFN receptor chain IFNAR1 also stimulated LINE-1 propagation in vitro. Finally, a greater accumulation of LINE-1 was found in mice that lack IFNAR1 compared with wild type mice. We propose that LINE-1-induced IFN plays an important role in restricting LINE-1 propagation and discuss the putative role of IFN in preserving the genome stability.
authors.affiliation: From the Departments of Animal Biology, School of Veterinary Medicine and.
authors.forename: Qiujing
authors.initials: Q
authors.lastname: Yu
authors.affiliation: From the Departments of Animal Biology, School of Veterinary Medicine and.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Carbone
authors.affiliation: From the Departments of Animal Biology, School of Veterinary Medicine and.
authors.forename: Yuliya V
authors.initials: YV
authors.lastname: Katlinskaya
authors.affiliation: From the Departments of Animal Biology, School of Veterinary Medicine and.
authors.forename: Hui
authors.initials: H
authors.lastname: Zheng
authors.affiliation: From the Departments of Animal Biology, School of Veterinary Medicine and.
authors.forename: Ke
authors.initials: K
authors.lastname: Zheng
authors.affiliation: From the Departments of Animal Biology, School of Veterinary Medicine and.
authors.forename: Mengcheng
authors.initials: M
authors.lastname: Luo
authors.affiliation: From the Departments of Animal Biology, School of Veterinary Medicine and.
authors.forename: P Jeremy
authors.initials: PJ
authors.lastname: Wang
authors.affiliation: Cancer Biology, Abramson Family Cancer Research Institute, Basser Research Center for BRCA, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Greenberg
authors.affiliation: From the Departments of Animal Biology, School of Veterinary Medicine and syfuchs@vet.upenn.edu.
authors.forename: Serge Y
authors.initials: SY
authors.lastname: Fuchs
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation; D042822:Genomic Instability; D006367:HeLa Cells; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D016899:Interferon-beta / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D061251:Primary Cell Culture; D020365:RNA Helicases / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D013737:Testis / Q000166:cytology / Q000276:immunology / Q000378:metabolism
chemical_list: C508032:Ifnar1 protein, mouse; D016898:Interferon-alpha; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta; C477006:Mov10l1 protein, mouse; D020365:RNA Helicases
keywords: DNA damage; LINE-1; genomic instability; interferon; radiation; receptor; retrotransposon; signaling