Format

Send to

Choose Destination
Cell. 2018 May 3;173(4):906-919.e13. doi: 10.1016/j.cell.2018.03.064. Epub 2018 Apr 26.

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

Author information

1
National Key Laboratory of Medical Molecular Biology, Department of Immunology & Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China.
2
MOH Key Laboratory of Human Disease Comparative Medicine, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing 100021, China.
3
National Key Laboratory of Medical Molecular Biology, Department of Immunology & Center for Immunotherapy, Institute of Basic Medical Sciences, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100005, China; National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai 200433, China; School of Medicine, Nankai University, Tianjin 300071, China. Electronic address: caoxt@immunol.org.

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.

KEYWORDS:

RIG-I; immune homeostasis; innate immunity; lncRNA; non-self RNA; pathogenic dsRNA; self regulation; type I interferons

PMID:
29706547
DOI:
10.1016/j.cell.2018.03.064

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center