Long noncoding RNA #32 contributes to antiviral responses by controlling interferon-stimulated gene expression

Significance Here, we describe a key feature of the long noncoding RNA (lncRNA) involved in innate immunity. We identified 182 lncRNAs that were highly modulated in poly(I:C)-treated hepatocyte cells. Of these, lncRNA#32 regulated the level of IFN-stimulated genes under both unstimulated and type I IFN-stimulated conditions through interactions with hnRNPU and ATF2, and therefore plays an important role in antiviral immunity. Despite the breadth of knowledge that exists regarding the function of long noncoding RNAs (lncRNAs) in biological phenomena, the role of lncRNAs in host antiviral responses is poorly understood. Here, we report that lncRNA#32 is associated with type I IFN signaling. The silencing of lncRNA#32 dramatically reduced the level of IFN-stimulated gene (ISG) expression, resulting in sensitivity to encephalomyocarditis virus (EMCV) infection. In contrast, the ectopic expression of lncRNA#32 significantly suppressed EMCV replication, suggesting that lncRNA#32 positively regulates the host antiviral response. We further demonstrated the suppressive function of lncRNA#32 in hepatitis B virus and hepatitis C virus infection. lncRNA#32 bound to activating transcription factor 2 (ATF2) and regulated ISG expression. Our results reveal a role for lncRNA#32 in host antiviral responses.

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