Cargando…
Endogenous Retrovirus-Derived Long Noncoding RNA Enhances Innate Immune Responses via Derepressing RELA Expression
Endogenous retroviruses (ERVs) are transposable elements that cause host genome instability and usually play deleterious roles in disease such as tumorigenesis. Recent advances also suggest that this “enemy within” may encode a viral mimic to induce antiviral immune responses through viral sensors....
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667616/ https://www.ncbi.nlm.nih.gov/pubmed/31363026 http://dx.doi.org/10.1128/mBio.00937-19 |
_version_ | 1783440061039116288 |
---|---|
author | Zhou, Bin Qi, Fei Wu, Fangyi Nie, Hongbo Song, Yifan Shao, Lu Han, Jingxuan Wu, Zhen Saiyin, Hexige Wei, Gang Wang, Penghua Ni, Ting Qian, Feng |
author_facet | Zhou, Bin Qi, Fei Wu, Fangyi Nie, Hongbo Song, Yifan Shao, Lu Han, Jingxuan Wu, Zhen Saiyin, Hexige Wei, Gang Wang, Penghua Ni, Ting Qian, Feng |
author_sort | Zhou, Bin |
collection | PubMed |
description | Endogenous retroviruses (ERVs) are transposable elements that cause host genome instability and usually play deleterious roles in disease such as tumorigenesis. Recent advances also suggest that this “enemy within” may encode a viral mimic to induce antiviral immune responses through viral sensors. Here, through whole-genome transcriptome analysis with RNA sequencing (RNA-Seq), we discovered that a full-length ERV-derived long noncoding RNA (lncRNA), designated lnc-EPAV (ERV-derived lncRNA positively regulates antiviral responses), was a positive regulator of NF-κB signaling. lnc-EPAV expression was rapidly upregulated by viral RNA mimics or RNA viruses to facilitate the expression of RELA, an NF-κB subunit that plays a crucial role in antiviral responses. Transcriptome analysis of lnc-EPAV-silenced macrophages showed that lnc-EPAV was critical for RELA target gene expression and innate immune responses. Consistently, lnc-EPAV-deficient mice exhibited reduced expression of type I interferons (IFNs) and, consequently, increased viral loads and mortality following lethal RNA virus infection. Mechanistically, lnc-EPAV promoted expression of RELA by competitively binding to and displacing SFPQ, a transcriptional repressor of Rela. Altogether, our work demonstrates an alternative mechanism by which ERVs regulate antiviral immune responses. |
format | Online Article Text |
id | pubmed-6667616 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-66676162019-08-06 Endogenous Retrovirus-Derived Long Noncoding RNA Enhances Innate Immune Responses via Derepressing RELA Expression Zhou, Bin Qi, Fei Wu, Fangyi Nie, Hongbo Song, Yifan Shao, Lu Han, Jingxuan Wu, Zhen Saiyin, Hexige Wei, Gang Wang, Penghua Ni, Ting Qian, Feng mBio Research Article Endogenous retroviruses (ERVs) are transposable elements that cause host genome instability and usually play deleterious roles in disease such as tumorigenesis. Recent advances also suggest that this “enemy within” may encode a viral mimic to induce antiviral immune responses through viral sensors. Here, through whole-genome transcriptome analysis with RNA sequencing (RNA-Seq), we discovered that a full-length ERV-derived long noncoding RNA (lncRNA), designated lnc-EPAV (ERV-derived lncRNA positively regulates antiviral responses), was a positive regulator of NF-κB signaling. lnc-EPAV expression was rapidly upregulated by viral RNA mimics or RNA viruses to facilitate the expression of RELA, an NF-κB subunit that plays a crucial role in antiviral responses. Transcriptome analysis of lnc-EPAV-silenced macrophages showed that lnc-EPAV was critical for RELA target gene expression and innate immune responses. Consistently, lnc-EPAV-deficient mice exhibited reduced expression of type I interferons (IFNs) and, consequently, increased viral loads and mortality following lethal RNA virus infection. Mechanistically, lnc-EPAV promoted expression of RELA by competitively binding to and displacing SFPQ, a transcriptional repressor of Rela. Altogether, our work demonstrates an alternative mechanism by which ERVs regulate antiviral immune responses. American Society for Microbiology 2019-07-30 /pmc/articles/PMC6667616/ /pubmed/31363026 http://dx.doi.org/10.1128/mBio.00937-19 Text en Copyright © 2019 Zhou et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Zhou, Bin Qi, Fei Wu, Fangyi Nie, Hongbo Song, Yifan Shao, Lu Han, Jingxuan Wu, Zhen Saiyin, Hexige Wei, Gang Wang, Penghua Ni, Ting Qian, Feng Endogenous Retrovirus-Derived Long Noncoding RNA Enhances Innate Immune Responses via Derepressing RELA Expression |
title | Endogenous Retrovirus-Derived Long Noncoding RNA Enhances Innate Immune Responses via Derepressing RELA Expression |
title_full | Endogenous Retrovirus-Derived Long Noncoding RNA Enhances Innate Immune Responses via Derepressing RELA Expression |
title_fullStr | Endogenous Retrovirus-Derived Long Noncoding RNA Enhances Innate Immune Responses via Derepressing RELA Expression |
title_full_unstemmed | Endogenous Retrovirus-Derived Long Noncoding RNA Enhances Innate Immune Responses via Derepressing RELA Expression |
title_short | Endogenous Retrovirus-Derived Long Noncoding RNA Enhances Innate Immune Responses via Derepressing RELA Expression |
title_sort | endogenous retrovirus-derived long noncoding rna enhances innate immune responses via derepressing rela expression |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6667616/ https://www.ncbi.nlm.nih.gov/pubmed/31363026 http://dx.doi.org/10.1128/mBio.00937-19 |
work_keys_str_mv | AT zhoubin endogenousretrovirusderivedlongnoncodingrnaenhancesinnateimmuneresponsesviaderepressingrelaexpression AT qifei endogenousretrovirusderivedlongnoncodingrnaenhancesinnateimmuneresponsesviaderepressingrelaexpression AT wufangyi endogenousretrovirusderivedlongnoncodingrnaenhancesinnateimmuneresponsesviaderepressingrelaexpression AT niehongbo endogenousretrovirusderivedlongnoncodingrnaenhancesinnateimmuneresponsesviaderepressingrelaexpression AT songyifan endogenousretrovirusderivedlongnoncodingrnaenhancesinnateimmuneresponsesviaderepressingrelaexpression AT shaolu endogenousretrovirusderivedlongnoncodingrnaenhancesinnateimmuneresponsesviaderepressingrelaexpression AT hanjingxuan endogenousretrovirusderivedlongnoncodingrnaenhancesinnateimmuneresponsesviaderepressingrelaexpression AT wuzhen endogenousretrovirusderivedlongnoncodingrnaenhancesinnateimmuneresponsesviaderepressingrelaexpression AT saiyinhexige endogenousretrovirusderivedlongnoncodingrnaenhancesinnateimmuneresponsesviaderepressingrelaexpression AT weigang endogenousretrovirusderivedlongnoncodingrnaenhancesinnateimmuneresponsesviaderepressingrelaexpression AT wangpenghua endogenousretrovirusderivedlongnoncodingrnaenhancesinnateimmuneresponsesviaderepressingrelaexpression AT niting endogenousretrovirusderivedlongnoncodingrnaenhancesinnateimmuneresponsesviaderepressingrelaexpression AT qianfeng endogenousretrovirusderivedlongnoncodingrnaenhancesinnateimmuneresponsesviaderepressingrelaexpression |