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

120 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
Cell Line
DEAD Box Protein 58/metabolism
Autophagy/immunology
Humans
RNA, Small Interfering/genetics
Membrane Proteins/genetics
Protein Binding/immunology
Cercopithecus aethiops
Vesicular stomatitis Indiana virus/immunology
RNA-Binding Proteins/metabolism
Animals
RNA Interference
HEK293 Cells
Signal Transduction/immunology
Interferon Type I/immunology
Cytokines/metabolism
Ubiquitins/metabolism
COS Cells

ASJC Scopus subject areas

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

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10.15252/embj.201796781

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@article{ccd9b18c1c3546f4b8ca58936480c51f,

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, Cell Line, DEAD Box Protein 58/metabolism, Autophagy/immunology, Humans, RNA, Small Interfering/genetics, Membrane Proteins/genetics, Protein Binding/immunology, Cercopithecus aethiops, Vesicular stomatitis Indiana virus/immunology, RNA-Binding Proteins/metabolism, Animals, RNA Interference, HEK293 Cells, Signal Transduction/immunology, Interferon Type I/immunology, Cytokines/metabolism, Ubiquitins/metabolism, COS Cells",

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",

month = feb,

day = "1",

doi = "10.15252/embj.201796781",

language = "English (US)",

volume = "37",

pages = "351--366",

journal = "EMBO Journal",

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TY - JOUR

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.

KW - ISG15

KW - LRRC25

KW - RIG-I

KW - p62

KW - selective autophagy

KW - Cell Line

KW - DEAD Box Protein 58/metabolism

KW - Autophagy/immunology

KW - Humans

KW - RNA, Small Interfering/genetics

KW - Membrane Proteins/genetics

KW - Protein Binding/immunology

KW - Cercopithecus aethiops

KW - Vesicular stomatitis Indiana virus/immunology

KW - RNA-Binding Proteins/metabolism

KW - Animals

KW - RNA Interference

KW - HEK293 Cells

KW - Signal Transduction/immunology

KW - Interferon Type I/immunology

KW - Cytokines/metabolism

KW - Ubiquitins/metabolism

KW - COS Cells

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U2 - 10.15252/embj.201796781

DO - 10.15252/embj.201796781

M3 - Article

C2 - 29288164

AN - SCOPUS:85039558340

SN - 0261-4189

VL - 37

SP - 351

EP - 366

JO - EMBO Journal

JF - EMBO Journal

IS - 3

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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