Nc886, a novel suppressor of the type i interferon response upon pathogen intrusion

Yeon Su Lee, Xiaoyong Bao, Hwi Ho Lee, Jiyoung Joan Jang, Enkhjin Saruuldalai, Gaeul Park, Wonkyun Ronny Im, Jong Lyul Park, Seon Young Kim, Sooyong Shin, Sung Ho Jeon, Sangmin Kang, Hyun Sung Lee, Ju Seog Lee, Ke Zhang, Eun Jung Park, In Hoo Kim, Yong Sun Lee

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Interferons (IFNs) are a crucial component in the innate immune response. Especially the IFN-β signaling operates in most cell types and plays a key role in the first line of defense upon pathogen intrusion. The induction of IFN-β should be tightly controlled, because its hyperactivation can lead to tissue damage or autoimmune diseases. Activation of the IFN-β promoter needs Interferon Regulatory Factor 3 (IRF3), together with Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Activator Protein 1 (AP-1). Here we report that a human noncoding RNA, nc886, is a novel suppressor for the IFN-β signaling and inflammation. Upon treatment with several pathogen-associated molecular patterns and viruses, nc886 suppresses the activation of IRF3 and also inhibits NF-κB and AP-1 via inhibiting Protein Kinase R (PKR). These events lead to decreased expression of IFN-β and resultantly IFN-stimulated genes. nc886 s role might be to restrict the IFN-β signaling from hyperactivation. Since nc886 expression is regulated by epigenetic and environmental factors, nc886 might explain why innate immune responses to pathogens are variable depending on biological settings.

    Original languageEnglish (US)
    Article number2003
    Pages (from-to)1-13
    Number of pages13
    JournalInternational journal of molecular sciences
    Volume22
    Issue number4
    DOIs
    StatePublished - Feb 2 2021

    Keywords

    • Interferon
    • Interferon Regulatory Factor 3
    • Nc886
    • Pathogen
    • Protein Kinase R

    ASJC Scopus subject areas

    • Catalysis
    • Molecular Biology
    • Spectroscopy
    • Computer Science Applications
    • Physical and Theoretical Chemistry
    • Organic Chemistry
    • Inorganic Chemistry

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