Endogenous Retrovirus-Derived Long Noncoding RNA Enhances Innate Immune Responses via Derepressing RELA Expression

MBio
Bin ZhouFeng Qian

Abstract

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 A...Continue Reading

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Citations

Sep 10, 2020·International Journal of Molecular Sciences·Beatriz SuarezPuri Fortes
Nov 4, 2020·RNA Biology·Katharina Walther, Leon N Schulte
Nov 13, 2020·Journal of Virology·Mingyue ChenLei Zhang
Apr 23, 2021·Journal of Virology·Smitha Srinivasachar Badarinarayan, Daniel Sauter

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Datasets Mentioned

BETA
PXD011577
PRJNA503657

Methods Mentioned

BETA
RNA-seq
PCR
ELISA
pulldown
immunoprecipitation
ChIP-seq
ChIP
Genotyping
RIP
RIP-seq

Software Mentioned

ChIPseeker R
BLAST
GSEA
LTR
Integrated Genome Browser
STAR
Gene tracks
RepeatMasker
Cuffdiff
OFFinder

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