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

doi:10.15252/embj.201796781

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 journal › Article › peer-review

95 Scopus citations

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.

Original language	English (US)
Pages (from-to)	351-366
Number of pages	16
Journal	EMBO Journal
Volume	37
Issue number	3
DOIs	https://doi.org/10.15252/embj.201796781
State	Published - Feb 1 2018

Keywords

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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10.15252/embj.201796781

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title = "LRRC25 inhibits type I IFN signaling by targeting ISG15-associated RIG-I for autophagic degradation",

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",

author = "Yang Du and Tianhao Duan and Yanchun Feng and Qingxiang Liu and Meng Lin and Jun Cui and Wang, {Rong Fu}",

note = "Funding Information: This work was supported by National Natural Science Foundation of China (91629101, 31522018), Guangdong Natural Science Funds for Distinguished Young Scholar (S2013050014772), Guangdong Innovative Research Team Program (NO. 2011Y035 and 201001Y0104687244), Guangzhou Science and Technology Project (201605030012), and the Training Program for Outstanding Young Teachers in Higher Education institutions of Guangdong Province (YQ2015001). The National Basic Research Program of China (973 Program) (2014CB745203), R.-F.W, was in part supported by grants (CA101795 and DA030338) from NCI and NIDA, NIH. Publisher Copyright: {\textcopyright} 2017 The Authors",

year = "2018",

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doi = "10.15252/embj.201796781",

language = "English (US)",

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T1 - LRRC25 inhibits type I IFN signaling by targeting ISG15-associated RIG-I for autophagic degradation

AU - Du, Yang

AU - Duan, Tianhao

AU - Feng, Yanchun

AU - Liu, Qingxiang

AU - Lin, Meng

AU - Cui, Jun

AU - Wang, Rong Fu

N1 - Funding Information: This work was supported by National Natural Science Foundation of China (91629101, 31522018), Guangdong Natural Science Funds for Distinguished Young Scholar (S2013050014772), Guangdong Innovative Research Team Program (NO. 2011Y035 and 201001Y0104687244), Guangzhou Science and Technology Project (201605030012), and the Training Program for Outstanding Young Teachers in Higher Education institutions of Guangdong Province (YQ2015001). The National Basic Research Program of China (973 Program) (2014CB745203), R.-F.W, was in part supported by grants (CA101795 and DA030338) from NCI and NIDA, NIH. Publisher Copyright: © 2017 The Authors

PY - 2018/2/1

Y1 - 2018/2/1

N2 - 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.

AB - 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.

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KW - LRRC25

KW - RIG-I

KW - p62

KW - selective autophagy

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ER -

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

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Keywords

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