title: A novel function of human Pumilio proteins in cytoplasmic sensing of viral infection.
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.
authors.affiliation: Laboratory of Molecular Genetics, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Narita
authors.affiliation: Laboratory of Molecular Genetics, Institute for Virus Research, Kyoto University, Kyoto, Japan; Institute for Innovative NanoBio Drug Discovery and Development, Graduate School of Pharmaceutical Science, Kyoto University, Kyoto, Japan.
authors.forename: Kiyohiro
authors.initials: K
authors.lastname: Takahasi
authors.affiliation: Laboratory of Molecular Genetics, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Etsu
authors.initials: E
authors.lastname: Murakami
authors.affiliation: Laboratory of Molecular Genetics, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Hirano
authors.affiliation: Laboratory of Molecular Genetics, Institute for Virus Research, Kyoto University, Kyoto, Japan.
authors.forename: Seiji P
authors.initials: SP
authors.lastname: Yamamoto
authors.affiliation: Division of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Yoneyama
authors.affiliation: Laboratory of Molecular Genetics, Institute for Virus Research, Kyoto University, Kyoto, Japan; Laboratory of Molecular Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kato
authors.affiliation: Laboratory of Molecular Genetics, Institute for Virus Research, Kyoto University, Kyoto, Japan; Laboratory of Molecular Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujita
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D003593:Cytoplasm / Q000378:metabolism*; D006801:Humans; D016899:Interferon-beta / Q000302:isolation & purification*; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D012327:RNA Virus Infections / Q000378:metabolism; D012330:RNA, Double-Stranded; D012367:RNA, Viral / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D000998:Antiviral Agents; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C465505:pumilio protein, human; D016899:Interferon-beta