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      Self-Recognition of an Inducible Host lncRNA by RIG-I Feedback Restricts Innate Immune Response

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          Abstract

          The innate RNA sensor RIG-I is critical in the initiation of antiviral type I interferons (IFNs) production upon recognition of "non-self" viral RNAs. Here, we identify a host-derived, IFN-inducible long noncoding RNA, lnc-Lsm3b, that can compete with viral RNAs in the binding of RIG-I monomers and feedback inactivate the RIG-I innate function at late stage of innate response. Mechanistically, binding of lnc-Lsm3b restricts RIG-I protein's conformational shift and prevents downstream signaling, thereby terminating type I IFNs production. Multivalent structural motifs and long-stem structure are critical features of lnc-Lsm3b for RIG-I binding and inhibition. These data reveal a non-canonical self-recognition mode in the regulation of immune response and demonstrate an important role of an inducible "self" lncRNA acting as a potent molecular decoy actively saturating RIG-I binding sites to restrict the duration of "non-self" RNA-induced innate immune response and maintaining immune homeostasis, with potential utility in inflammatory disease management.

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          Author and article information

          Journal
          Cell
          Cell
          Elsevier BV
          00928674
          May 2018
          May 2018
          : 173
          : 4
          : 906-919.e13
          Article
          10.1016/j.cell.2018.03.064
          29706547
          df89dd68-11f4-4985-97f0-3ad5ae8336c1
          © 2018

          http://www.elsevier.com/tdm/userlicense/1.0/

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