The cytosolic nucleic acid sensor LRRFIP1 mediates the production of type I interferon via a beta-catenin-dependent pathway

Nat Immunol. 2010 Jun;11(6):487-94. doi: 10.1038/ni.1876. Epub 2010 May 9.


Intracellular nucleic acid sensors detect microbial RNA and DNA and trigger the production of type I interferon. However, the cytosolic nucleic acid-sensing system remains to be fully identified. Here we show that the cytosolic nucleic acid-binding protein LRRFIP1 contributed to the production of interferon-beta (IFN-beta) induced by vesicular stomatitis virus (VSV) and Listeria monocytogenes in macrophages. LRRFIP1 bound exogenous nucleic acids and increased the expression of IFN-beta induced by both double-stranded RNA and double-stranded DNA. LRRFIP1 interacted with beta-catenin and promoted the activation of beta-catenin, which increased IFN-beta expression by binding to the C-terminal domain of the transcription factor IRF3 and recruiting the acetyltransferase p300 to the IFN-beta enhanceosome via IRF3. Therefore, LRRFIP1 and its downstream partner beta-catenin constitute another coactivator pathway for IRF3-mediated production of type I interferon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cells, Cultured
  • Cytosol / physiology*
  • DNA, Viral / genetics
  • DNA, Viral / immunology
  • Humans
  • Interferon Regulatory Factor-3 / metabolism
  • Interferon Type I / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • RNA-Binding Proteins / metabolism*
  • Receptors, Pattern Recognition / genetics
  • Receptors, Pattern Recognition / immunology
  • Signal Transduction*
  • beta Catenin / metabolism


  • DNA, Viral
  • Interferon Regulatory Factor-3
  • Interferon Type I
  • Irf3 protein, mouse
  • LRRFIP1 protein, human
  • RNA-Binding Proteins
  • Receptors, Pattern Recognition
  • beta Catenin