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Lnc-EAPV binding proteins in C57BL/6J BMDMs

ABSTRACT: 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-κB signaling. Lnc-EPAV expression was rapidly up-regulated by viral RNA mimic or RNA viruses to facilitate the expression of RELA, an NF-κB 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. The binding between ERV-derived RNAs and SFPQ also existed in human cells. Altogether, our work demonstrates an alternative mechanism by which ERVs regulate antiviral immune responses.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Macrophage

SUBMITTER: Bin Zhou

LAB HEAD: Feng Qian

PROVIDER: PXD011577 | Pride | 2018-11-07

REPOSITORIES: Pride

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			Action	DRS
	Orbi05969-lnc-EAPV.raw	Raw
	Orbi05969-lnc-EPAV.msf	Msf
	Orbi07148-lnc-EAPVE2.raw	Raw
	Orbi07148-lnc-EPAVE2.msf	Msf

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