title: Ubiquitin-mediated modulation of the cytoplasmic viral RNA sensor RIG-I.
abstract: RIG-I-like receptors, including RIG-I, MDA5 and LGP2, recognize cytoplasmic viral RNA. The RIG-I protein consists of N-terminal CARDs, central RNA helicase and C-terminal domains. RIG-I activation is regulated by ubiquitination. Three ubiquitin ligases target the RIG-I protein. TRIM25 and Riplet ubiquitin ligases are positive regulators of RIG-I and deliver the K63-linked polyubiquitin moiety to RIG-I CARDs and the C-terminal domain. RNF125, another ubiquitin ligase, is a negative regulator of RIG-I and mediates K48-linked polyubiquitination of RIG-I, leading to the degradation of the RIG-I protein by proteasomes. The K63-linked polyubiquitin chains of RIG-I are removed by a deubiquitin enzyme, CYLD. Thus, CYLD is a negative regulator of RIG-I. Furthermore, TRIM25 itself is regulated by ubiquitination. HOIP and HOIL proteins are ubiquitin ligases and are also known as linear ubiquitin assembly complexes (LUBACs). The TRIM25 protein is ubiquitinated by LUBAC and then degraded by proteasomes. The splice variant of RIG-I encodes a protein that lacks the first CARD of RIG-I, and the variant RIG-I protein is not ubiquitinated by TRIM25. Therefore, ubiquitin is the key regulator of the cytoplasmic viral RNA sensor RIG-I.
authors: Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku Sapporo 060-8638, Japan. oshiumi@med.hokudai.ac.jp
authors: Hiroyuki
authors: H
authors: Oshiumi
authors: Misako
authors: M
authors: Matsumoto
authors: Tsukasa
authors: T
authors: Seya
mesh_terms: D017398:Alternative Splicing; D003593:Cytoplasm / Q000378:metabolism / Q000821:virology; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D008954:Models, Biological; D012367:RNA, Viral / Q000378:metabolism*; D011971:Receptors, Immunologic; D014157:Transcription Factors / Q000378:metabolism*; D000070584:Tripartite Motif Proteins; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D012367:RNA, Viral; D011971:Receptors, Immunologic; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D025801:Ubiquitin; C084523:TRIM25 protein, human; D044767:Ubiquitin-Protein Ligases; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases