Mus musculus Homo sapiens Raw sequence reads

Endogenous retroviruses (ERVs) are transposable elements that cause host genome instability and usually play deleterious roles such as tumorigenesis. Recent advances also suggest that this 'enemy within' may encode viral mimic to induce antiviral immune responses through viral sensors. Here, through whole genome RNA-seq we discovered a full-length ERV-derived long non-coding RNA (lncRNA), designated lnc-EPAV (ERV-derived lncRNA positively regulates antiviral responses), as a positive regulator of NF-?B signaling. lnc-EPAV expression was rapidly up-regulated by viral RNA mimic or RNA viruses to facilitate the expression of RELA, an NF-?B subunit that plays a critical role in antiviral responses. In turn, RELA promoted the transcription of lnc-EPAV to form a positive feedback loop. Transcriptome analysis of lnc-EPAV-silenced macrophages, combined with gain- and loss-of-function experiments, showed that lnc-EPAV was critical for induction of type I interferon (IFN) and inflammatory cytokine expression by RNA viruses. Consistently, lnc-EPAV-deficient mice exhibited reduced expression of type I 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, examined by ChIP-seq and ChIP-PCR. The binding between ERV-derived RNAs and SFPQ also existed in human cells by RIP-seq analysis. Altogether, our work demonstrates an alternative mechanism by which ERVs regulate antiviral immune responses.

Identifier
Source https://data.blue-cloud.org/search-details?step=~012A3EC28EFC5213C7956811EB5AD54C10EABF79F03
Metadata Access https://data.blue-cloud.org/api/collections/A3EC28EFC5213C7956811EB5AD54C10EABF79F03
Provenance
Instrument HiSeq X Ten; ILLUMINA
Publisher Blue-Cloud Data Discovery & Access service; ELIXIR-ENA
Publication Year 2024
OpenAccess true
Contact blue-cloud-support(at)maris.nl
Representation
Discipline Marine Science
Temporal Coverage Begin 2013-05-13T00:00:00Z
Temporal Coverage End 2019-07-14T00:00:00Z