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

Nat Immunol. 2019 Jul;20(7):812-823. doi: 10.1038/s41590-019-0379-0. Epub 2019 Apr 29.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • DEAD Box Protein 58 / genetics*
  • DNA-Binding Proteins / genetics*
  • Gene Expression Regulation*
  • Host-Pathogen Interactions / genetics*
  • Host-Pathogen Interactions / immunology*
  • Humans
  • Immunity, Innate / genetics*
  • Macrophages, Peritoneal / immunology
  • Macrophages, Peritoneal / metabolism
  • Macrophages, Peritoneal / virology
  • Mice
  • Models, Biological
  • RNA Interference
  • RNA Viruses / immunology
  • RNA, Long Noncoding / genetics*
  • Signal Transduction
  • Transcription Factors / genetics*
  • Virus Diseases / genetics
  • Virus Diseases / immunology
  • Virus Diseases / metabolism
  • Virus Diseases / virology

Substances

  • DNA-Binding Proteins
  • RNA, Long Noncoding
  • Transcription Factors
  • Trim25 protein, mouse
  • Ddx58 protein, mouse
  • DEAD Box Protein 58