Pasquesi Giulia Irene Maria, Kelly Conor J, Ordonez Andrea D, Chuong Edward B
BioFrontiers Institute and Department of Molecular, Cellular & Developmental Biology, University of Colorado Boulder, 596 UCB, Boulder, CO, 80309, USA.
Mob DNA. 2022 Sep 6;13(1):22. doi: 10.1186/s13100-022-00277-z.
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.
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.
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.
蝙蝠是动物源性病毒的主要宿主,人们对表征蝙蝠先天免疫和炎症的特异性特征的兴趣与日俱增。最近的研究揭示了影响干扰素(IFN)信号传导和IFN刺激基因(ISG)的蝙蝠特异性适应性,但我们对塑造蝙蝠免疫进化的遗传机制仍了解有限。在此,我们使用RNA测序和CUT&RUN技术,研究了小棕蝠(Myotis lucifugus)原代胚胎成纤维细胞在I型干扰素反应过程中转座元件(TE)的转录和表观遗传动态。
我们发现多个蝙蝠特异性TE在响应IFN时经历了位点特异性和家族水平的转录诱导。我们的转录组重新组装鉴定出多个从蝙蝠特异性TE获得新外显子的ISG,包括NLRC5、SLNF5和IFITM2基因的一个先前未注释的异构体。我们还鉴定了TE衍生调控元件的实例,但未找到强有力的证据支持TE在响应IFN时发生全基因组表观遗传激活。
总体而言,我们的研究揭示了在小棕蝠细胞中由IFN诱导的众多TE衍生转录本、蛋白质和可变异构体,突出了可能有助于蝙蝠特异性免疫功能的候选位点。