The long noncoding RNA Lnczc3h7a promotes a TRIM25-mediated RIG-I antiviral innate immune response

• Published in: Nature immunology Vol. 20; no. 7; pp. 812 - 823
• Main Authors: Lin, Hongyu, Jiang, Minghong, Liu, Lun, Yang, Zongheng, Ma, Zhongfei, Liu, Shuo, Ma, Yuanwu, Zhang, Lianfeng, Cao, Xuetao
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.07.2019; Nature Publishing Group
• Subjects: 631/250; 692/699; Animals; Antiviral agents; Biomedical and Life Sciences; Biomedicine; Cell Line; Cellular signal transduction; DEAD Box Protein 58 - genetics; Depletion; DNA helicase; DNA-Binding Proteins - genetics; Gene Expression Regulation; Host-Pathogen Interactions - genetics; Host-Pathogen Interactions - immunology; Humans; Immune response; Immunity, Innate - genetics; Immunology; Infectious Diseases; Innate immunity; Macrophages, Peritoneal - immunology; Macrophages, Peritoneal - metabolism; Macrophages, Peritoneal - virology; Mice; Models, Biological; RNA Interference; RNA viruses; RNA Viruses - immunology; RNA, Long Noncoding - genetics; Signal Transduction; Transcription Factors - genetics; Ubiquitin; Ubiquitin-protein ligase; Ubiquitination; Virus Diseases - genetics; Virus Diseases - immunology; Virus Diseases - metabolism; Virus Diseases - virology; China
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/s41590-019-0379-0

The helicase RIG-I initiates an antiviral immune response after recognition of pathogenic RNA. TRIM25, an E3 ubiquitin ligase, mediates K63-linked ubiquitination of RIG-I, which is crucial for RIG-I downstream signaling and the antiviral innate immune response. The components and mode of the RIG-I-initiated innate signaling remain to be fully understood. Here we identify a novel long noncoding RNA (Lnczc3h7a) that binds to TRIM25 and promotes RIG-I-mediated antiviral innate immune responses. Depletion of Lnczc3h7a impairs RIG-I signaling and the antiviral innate response to RNA viruses in vitro and in vivo. Mechanistically, Lnczc3h7a binds to both TRIM25 and activated RIG-I, serving as a molecular scaffold for stabilization of the RIG-I–TRIM25 complex at the early stage of viral infection. Lnczc3h7a facilitates TRIM25-mediated K63-linked ubiquitination of RIG-I and thus promotes downstream signaling transduction. Our findings reveal that host RNAs can enhance the response of innate immune sensors to foreign RNAs, ensuring effective antiviral defense. RIG-I is an RNA sensor and is required for effective antiviral immunity. Cao and colleagues demonstrate that the previously undescribed long noncoding RNA Lnczc3h7a serves an essential scaffolding role in supporting productive RIG-I signaling.