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

PLoS Pathog. 2014 Oct 23;10(10):e1004417. doi: 10.1371/journal.ppat.1004417. eCollection 2014 Oct.

Abstract

RIG-I-like receptor (RLR) plays a pivotal role in the detection of invading pathogens to initiate type I interferon (IFN) gene transcription. Since aberrant IFN production is harmful, RLR signaling is strictly regulated. However, the regulatory mechanisms are not fully understood. By expression cloning, we identified Pumilio proteins, PUM1 and PUM2, as candidate positive regulators of RIG-I signaling. Overexpression of Pumilio proteins and their knockdown augmented and diminished IFN-β promoter activity induced by Newcastle disease virus (NDV), respectively. Both proteins showed a specific association with LGP2, but not with RIG-I or MDA5. Furthermore, all of these components were recruited to NDV-induced antiviral stress granules. Interestingly, biochemical analyses revealed that Pumilio increased double-stranded (ds) RNA binding affinity of LGP2; however, Pumilio was absent in the dsRNA-LGP2 complex, suggesting that Pumilio facilitates viral RNA recognition by LGP2 through its chaperon-like function. Collectively, our results demonstrate an unknown function of Pumilio in viral recognition by LGP2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology*
  • Cytoplasm / metabolism*
  • Humans
  • Interferon-beta / isolation & purification*
  • Promoter Regions, Genetic / drug effects*
  • RNA Virus Infections / metabolism
  • RNA, Double-Stranded
  • RNA, Viral / metabolism
  • RNA-Binding Proteins / metabolism*
  • Signal Transduction / immunology
  • Transcription Factors / metabolism*

Substances

  • Antiviral Agents
  • RNA, Double-Stranded
  • RNA, Viral
  • RNA-Binding Proteins
  • Transcription Factors
  • pumilio protein, human
  • Interferon-beta

Grant support

This work was supported by independent grants from Japan Science and Technology Agency (PRESTO), from Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan (innovative areas, infection competency, no. 24115004 and scientific research A, no. 23249023), from Daiichi Sankyo Foundation of Life Science, and from the Takeda Science Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.