2. Academic Validation
  3. LRRC25 inhibits type I IFN signaling by targeting ISG15-associated RIG-I for autophagic degradation

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

  • EMBO J. 2018 Feb 1;37(3):351-366. doi: 10.15252/embj.201796781.
Yang Du 1 2,  Tianhao Duan 1 2,  Yanchun Feng 1 2,  Qingxiang Liu 2,  Meng Lin 2,  Jun Cui 3 2,  Rong-Fu Wang 4 5 6
Affiliations

Affiliations

  • 1 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
  • 2 Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China.
  • 3 Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China [email protected] [email protected].
  • 4 Center for Inflammation and Epigenetics, Houston Methodist Research Institute, Houston, TX, USA [email protected] [email protected].
  • 5 Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA.
  • 6 Institute of Biosciences and Technology, College of Medicine, Texas A & M University, Houston, TX, USA.
PMID: 29288164 DOI: 10.15252/embj.201796781
Abstract

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.

Keywords

ISG15; LRRC25; RIG‐I; p62; selective autophagy.

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