Sensing of transposable elements by the antiviral innate immune system Gázquez Gutiérrez, Ana Witteveldt, Jeroen Rodríguez Heras, Sara Macías, Sara Mobile genetic elements Transposable elements Type I interferon Nucleic acid sensing Antiviral immunity We thank Dr. Francisco Sanchez-Luque, Dr. Martin Reijns, and Priscilla Chin for helpful discussions and comments on the manuscript. This work was funded by grants from the Wellcome Trust 107665/Z/15/Z and Royal Society grant RGS\R1\191368 to S.M., and from MINECO SAF2015-71589-P and Ramon y Cajal grant RYC-2016-21395 to S.R.H. Figures were designed using Smart Servier Medical Art (https://smart.servier.com). Around half of the genomes in mammals are composed of transposable elements (TEs) such as DNA transposons and retrotransposons. Several mechanisms have evolved to prevent their activity and the detrimental impact of their insertional mutagenesis. Despite these potentially negative effects, TEs are essential drivers of evolution, and in certain settings, beneficial to their hosts. For instance, TEs have rewired the antiviral gene regulatory network and are required for early embryonic development. However, due to structural similarities between TE-derived and viral nucleic acids, cells can misidentify TEs as invading viruses and trigger the major antiviral innate immune pathway, the type I interferon (IFN) response. This review will focus on the different settings in which the role of TE-mediated IFN activation has been documented, including cancer and senescence. Importantly, TEs may also play a causative role in the development of complex autoimmune diseases characterized by constitutive type I IFN activation. All these observations suggest the presence of strong but opposing forces driving the coevolution of TEs and antiviral defense. A better biological understanding of the TE replicative cycle as well as of the antiviral nucleic acid sensing mechanisms will provide insights into how these two biological processes interact and will help to design better strategies to treat human diseases characterized by aberrant TE expression and/ or type I IFN activation. 2021-10-08T10:47:28Z 2021-10-08T10:47:28Z 2021-04-22 journal article Gázquez-Gutiérrez, A... [et al.] (2021). Sensing of transposable elements by the antiviral innate immune system. RNA, 27(7), 735-752. doi:[10.1261/rna.078721.121] http://hdl.handle.net/10481/70753 10.1261/rna.078721.121 eng http://creativecommons.org/licenses/by/3.0/es/ open access Atribución 3.0 España Cold Spring Harbor