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.
Highlights
Type 1 interferons (IFN1) mediate defense against viruses but their role in regulating retrotransposon activities is unknown
Long Interspersed Element-1 (LINE-1) Activities Stimulate IFN Expression and Signaling— We have previously reported a high level of LINE-1 mRNA expression in testes from mice whose spermatocytes lack MOV10L1 [14], RNA helicase, which is essential for silencing retrotransposons in the mouse male germline [14, 22, 23]
We propose that activation of LINE-1 triggers expression of low levels of IFN, which, in turn, restricts subsequent LINE-1 retrotransposition
Summary
Type 1 interferons (IFN1) mediate defense against viruses but their role in regulating retrotransposon activities is unknown. Results: LINE-1 retrotransposon induces IFN1, which in turn inhibits LINE-1 retrotransposition. Conclusion: IFN1 regulate activities and propagation of LINE-1. Type I interferons (IFN) including IFN␣ and IFN are critical for the cellular defense against viruses. We report that increased levels of IFN 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 IFN and of IFN-stimulated genes. The efficacy of LINE-1 replication was increased in isogenic cell lines harboring inactivating mutations in diverse elements of the IFN signaling pathway. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
