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

Author:
Jiang, Minghong, Zhang, Shikun, Yang, Zongheng, Lin, Hongyu, Zhu, Jun, Liu, Lun, Wang, Wendie, Liu, Shuo, Liu, Wei, Ma, Yuanwu, Zhang, Lianfeng, Cao, Xuetao
Source:
Cell 2018 v.173 no.4 pp. 906-919.e13
ISSN:
0092-8674
Subject:
binding sites, disease control, homeostasis, immune response, innate immunity, interferons, non-coding RNA
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.
Agid:
6335806