Transcriptional dynamics of transposable elements in the type I IFN response in Myotis lucifugus cells

ABSTRACT Background Bats are a major reservoir of zoonotic viruses, and there has been growing interest in characterizing bat-specific features of innate immunity and inflammation. Recent studies have revealed bat-specific adaptations affecting interferon (IFN) signaling and IFN- stimulated genes (ISGs), but we still have a limited understanding of the genetic mechanisms that have shaped the evolution of bat immunity. Here we investigated the transcriptional and epigenetic dynamics of transposable elements (TEs) during the type I IFN response in little brown bat ( Myotis lucifugus ) primary embryonic fibroblast cells, using RNA-seq and CUT&RUN. Results We found multiple bat-specific TEs that undergo both locus-specific and family-level transcriptional induction in response to IFN. Our transcriptome reassembly identified multiple ISGs that have acquired novel exons from bat-specific TEs, including NLRC5 , SLNF5 and a previously unannotated isoform of the IFITM2 gene. We also identified examples of TE-derived regulatory elements, but did not find strong evidence supporting genome-wide epigenetic activation of TEs in response to IFN. Conclusion Collectively, our study uncovers numerous TE-derived transcripts, proteins, and alternative isoforms that are induced by IFN in Myotis lucifugus cells, highlighting candidate loci that may contribute to bat-specific immune function.