SUMOylation of DDX39A Alters Binding and Export of Antiviral Transcripts to Control Innate Immunity

J Immunol. 2020 Jul 1;205(1):168-180. doi: 10.4049/jimmunol.2000053. Epub 2020 May 11.

Abstract

The RNA helicase DDX39A plays an important role in the RNA splicing/export process. In our study, human DDX39A facilitated RNA virus escape from innate immunity to promote virus proliferation by trapping TRAF3, TRAF6, and MAVS mRNAs in the HEK293T cell nucleus. DDX39A was a target for SUMOylation. SUMO1, 2, and 3 modifications were found on immunoprecipitated DDX39A. However, only the SUMO1 modification decreased in vesicular stomatitis virus-infected HEK293T cells. Further studies have found that viral infection reduced SUMO1 modification of DDX39A and enhanced its ability to bind innate immunity-associated mRNAs by regulating the abundance of RanBP2 with SUMO1 E3 ligase activity. RanBP2 acted as an E3 SUMO ligase of DDX39A, which enhanced SUMO1 modification of DDX39A and attenuated its ability to bind RNA. This work described that specific mRNAs encoding antiviral signaling components were bound and sequestered in the nucleus by DDX39A to limit their expression, which proposed a new protein SUMOylation model to regulate innate immunity in viral infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Animals
  • Cell Nucleus / metabolism
  • Chlorocebus aethiops
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism*
  • Down-Regulation
  • Encephalomyocarditis virus / genetics
  • Encephalomyocarditis virus / immunology
  • Gene Expression Regulation / immunology*
  • Gene Knockout Techniques
  • HEK293 Cells
  • HeLa Cells
  • Host Microbial Interactions / genetics
  • Host Microbial Interactions / immunology
  • Humans
  • Immunity, Innate / genetics*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Molecular Chaperones / genetics
  • Nuclear Pore Complex Proteins / genetics
  • RNA Virus Infections / immunology*
  • RNA Virus Infections / virology
  • RNA, Messenger / metabolism
  • RNA, Viral / immunology
  • RNA, Viral / metabolism
  • SUMO-1 Protein / metabolism
  • Sendai virus / genetics
  • Sendai virus / immunology
  • Sumoylation / immunology
  • TNF Receptor-Associated Factor 3 / genetics
  • Transcription, Genetic / immunology
  • Vero Cells
  • Vesiculovirus / genetics
  • Vesiculovirus / immunology
  • Virus Replication / immunology

Substances

  • Adaptor Proteins, Signal Transducing
  • Intracellular Signaling Peptides and Proteins
  • MAVS protein, human
  • Molecular Chaperones
  • Nuclear Pore Complex Proteins
  • RNA, Messenger
  • RNA, Viral
  • SUMO-1 Protein
  • SUMO1 protein, human
  • TNF Receptor-Associated Factor 3
  • TRAF3 protein, human
  • Tifab protein, human
  • ran-binding protein 2
  • DDX39A protein, human
  • DEAD-box RNA Helicases