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A novel function of human Pumilio proteins in cytoplasmic sensing of viral infection

Ryo Narita1, Kiyohiro Takahasi2, Etsu Murakami1

  • 1Laboratory of Molecular Genetics, Institute for Virus Research, Kyoto University, Kyoto, Japan.

Plos Pathogens
|October 24, 2014
PubMed

Insights

Pumilio proteins (PUM1 and PUM2) enhance RIG-I-like receptor (RLR) signaling by aiding LGP2 in recognizing viral RNA. This discovery reveals a novel role for Pumilio in innate antiviral immunity.

Area of Science:

  • Immunology
  • Molecular Biology
  • Virology

Background:

  • RIG-I-like receptors (RLRs) are crucial for detecting viral pathogens and initiating type I interferon (IFN) production.
  • Strict regulation of RLR signaling is essential to prevent harmful aberrant IFN production, but regulatory mechanisms remain incompletely understood.

Purpose of the Study:

  • To identify novel positive regulators of RIG-I signaling.
  • To elucidate the function of Pumilio proteins in the context of RLR-mediated antiviral responses.

Main Methods:

  • Expression cloning was used to identify candidate regulators.
  • Newcastle disease virus (NDV) was used to induce IFN-β promoter activity.
  • Co-immunoprecipitation and immunofluorescence microscopy were employed to assess protein interactions and localization.

Main Results:

  • Pumilio proteins (PUM1 and PUM2) were identified as positive regulators of RIG-I signaling.
  • Pumilio overexpression enhanced, while knockdown diminished, NDV-induced IFN-β promoter activity.
  • Pumilio proteins specifically associated with LGP2 and were recruited to antiviral stress granules upon NDV infection.
  • Biochemical analyses indicated Pumilio enhances LGP2's double-stranded RNA binding affinity, suggesting a chaperon-like role in viral RNA recognition.

Conclusions:

  • Pumilio proteins play an uncharacterized role in viral recognition by LGP2.
  • Pumilio proteins act as positive regulators of RLR signaling, contributing to innate antiviral immunity.

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