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

First Author  Jiang M Year  2018
Journal  Cell Volume  173
Issue  4 Pages  906-919.e13
PubMed ID  29706547 Mgi Jnum  J:262834
Mgi Id  MGI:6160609 Doi  10.1016/j.cell.2018.03.064
Citation  Jiang M, et al. (2018) Self-Recognition of an Inducible Host lncRNA by RIG-I Feedback Restricts Innate Immune Response. Cell 173(4):906-919.e13
abstractText  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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