LRRC25 inhibits type I IFN signaling by targeting ISG15-associated RIG-I for autophagic degradation

Yang Du, Tianhao Duan, Yanchun Feng, Qingxiang Liu, Meng Lin, Jun Cui, Rong Fu Wang

Research output: Contribution to journalArticlepeer-review

95 Scopus citations


The RIG-I-like receptors (RLRs) are critical for protection against RNA virus infection, and their activities must be stringently controlled to maintain immune homeostasis. Here, we report that leucine-rich repeat containing protein 25 (LRRC25) is a key negative regulator of RLR-mediated type I interferon (IFN) signaling. Upon RNA virus infection, LRRC25 specifically binds to ISG15-associated RIG-I to promote interaction between RIG-I and the autophagic cargo receptor p62 and to mediate RIG-I degradation via selective autophagy. Depletion of either LRRC25 or ISG15 abrogates RIG-I-p62 interaction as well as the autophagic degradation of RIG-I. Collectively, our findings identify a previously unrecognized role of LRRC25 in type I IFN signaling activation by which LRRC25 acts as a secondary receptor to assist RIG-I delivery to autophagosomes for degradation in a p62-dependent manner.

Original languageEnglish (US)
Pages (from-to)351-366
Number of pages16
JournalEMBO Journal
Issue number3
StatePublished - Feb 1 2018


  • ISG15
  • LRRC25
  • RIG-I
  • p62
  • selective autophagy

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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