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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....

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Autores principales: 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
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
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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.
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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
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