NSUN5 Facilitates Viral RNA Recognition by RIG-I Receptor

J Immunol. 2020 Dec 15;205(12):3408-3418. doi: 10.4049/jimmunol.1901455. Epub 2020 Nov 11.

Abstract

The RIG-I receptor induces the innate antiviral responses upon sensing RNA viruses. The mechanisms through which RIG-I optimizes the strength of the downstream signaling remain incompletely understood. In this study, we identified that NSUN5 could potentiate the RIG-I innate signaling pathway. Deficiency of NSUN5 enhanced RNA virus proliferation and inhibited the induction of the downstream antiviral genes. Consistently, NSUN5-deficient mice were more susceptible to RNA virus infection than their wild-type littermates. Mechanistically, NSUN5 bound directly to both viral RNA and RIG-I, synergizing the recognition of dsRNA by RIG-I. Collectively, to our knowledge, this study characterized NSUN5 as a novel RIG-I coreceptor, playing a vital role in restricting RNA virus infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chlorocebus aethiops
  • DEAD Box Protein 58 / immunology*
  • HEK293 Cells
  • Humans
  • Immunity, Innate
  • Methyltransferases / immunology*
  • Mice
  • Muscle Proteins / immunology*
  • RNA Virus Infections / immunology*
  • RNA Viruses / immunology*
  • RNA, Double-Stranded / immunology*
  • RNA, Viral / immunology*
  • Receptors, Immunologic / immunology*
  • Vero Cells
  • tRNA Methyltransferases / immunology*

Substances

  • Muscle Proteins
  • RNA, Double-Stranded
  • RNA, Viral
  • Receptors, Immunologic
  • Methyltransferases
  • NSUN5 protein, human
  • Nsun5 protein, mouse
  • tRNA Methyltransferases
  • RIGI protein, human
  • Ddx58 protein, mouse
  • DEAD Box Protein 58