title: ARF-like protein 16 (ARL16) inhibits RIG-I by binding with its C-terminal domain in a GTP-dependent manner.
abstract: Retinoic acid-inducible gene I (RIG-I) recognizes RNA virus-derived nucleic acids, which leads to the production of type I interferon (IFN) in most cell types. Tight regulation of RIG-I activity is important to prevent ultra-immune responses. In this study, we identified an ARF-like (ARL) family member, ARL16, as a protein that interacts with RIG-I. Overexpression of ARL16, but not its homologous proteins ARL1 and ARF1, inhibited RIG-I-mediated downstream signaling and antiviral activity. Knockdown of endogenous ARL16 by RNAi potentiated Sendai virus-induced IFN-β expression and vesicular stomatitis virus replication. ARL16 interacted with the C-terminal domain (CTD) of RIG-I to suppress the association between RIG-I and RNA. ARL16 (T37N) and ARL16Δ45-54, which were restricted to the GTP-disassociated form, did not interact with RIG-I and also lost the inhibitory function. Furthermore, we suggest that endogenous ARL16 changes to GTP binding status upon viral infection and binds with the RIG-I CTD to negatively control its signaling activity. These findings suggested a novel innate immune function for an ARL family member, and a GTP-dependent model in which RIG-I is regulated.
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of Ministry of Education, College of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Yong-Kang
authors.initials: YK
authors.lastname: Yang
authors.forename: Hong
authors.initials: H
authors.lastname: Qu
authors.forename: Dong
authors.initials: D
authors.lastname: Gao
authors.forename: Wei
authors.initials: W
authors.lastname: Di
authors.forename: Hai-Wei
authors.initials: HW
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Guo
authors.forename: Zhong-He
authors.initials: ZH
authors.lastname: Zhai
authors.forename: Dan-Ying
authors.initials: DY
authors.lastname: Chen
mesh_terms: D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006160:Guanosine Triphosphate / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D016899:Interferon-beta / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D017434:Protein Structure, Tertiary; D012367:RNA, Viral / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic; D029082:Sendai virus / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017384:Sequence Deletion; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D012367:RNA, Viral; D011971:Receptors, Immunologic; D016899:Interferon-beta; D006160:Guanosine Triphosphate; C452820:RIGI protein, human; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D020727:ADP-Ribosylation Factors