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大足鼠耳蝠细胞中I型干扰素反应中转座元件的转录动力学

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

作者信息

Pasquesi Giulia Irene Maria, Kelly Conor J, Ordonez Andrea D, Chuong Edward B

机构信息

BioFrontiers Institute and Department of Molecular, Cellular & Developmental Biology, University of Colorado Boulder, 596 UCB, Boulder, CO, 80309, USA.

出版信息

Mob DNA. 2022 Sep 6;13(1):22. doi: 10.1186/s13100-022-00277-z.

DOI:10.1186/s13100-022-00277-z
PMID:36068622
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9446614/
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.

摘要

背景

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。

结果

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。

结论

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83f3/9446785/e48bd6119513/13100_2022_277_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83f3/9446785/f43dc65eb6b2/13100_2022_277_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83f3/9446785/2a27b4154e4d/13100_2022_277_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83f3/9446785/73f6b6d33f6a/13100_2022_277_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83f3/9446785/8f128405d84e/13100_2022_277_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83f3/9446785/e48bd6119513/13100_2022_277_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83f3/9446785/f43dc65eb6b2/13100_2022_277_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83f3/9446785/2a27b4154e4d/13100_2022_277_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83f3/9446785/73f6b6d33f6a/13100_2022_277_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83f3/9446785/8f128405d84e/13100_2022_277_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83f3/9446785/e48bd6119513/13100_2022_277_Fig5_HTML.jpg

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