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

Jiang M1, Zhang S1, Yang Z1, Lin H1, Zhu J1, Liu L1, Wang W1, Liu S1, Liu W1, Ma Y2, Zhang L2, Cao X3

Cell. 2018 Apr 23. pii: S0092-8674(18)30396-9.

PMID: 29706547

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.