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

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 clon...

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Main Authors: Ryo Narita, Kiyohiro Takahasi, Etsu Murakami, Emi Hirano, Seiji P Yamamoto, Mitsutoshi Yoneyama, Hiroki Kato, Takashi Fujita
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-10-01
Series:PLoS Pathogens
Online Access:http://europepmc.org/articles/PMC4207803?pdf=render
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author Ryo Narita
Kiyohiro Takahasi
Etsu Murakami
Emi Hirano
Seiji P Yamamoto
Mitsutoshi Yoneyama
Hiroki Kato
Takashi Fujita
author_facet Ryo Narita
Kiyohiro Takahasi
Etsu Murakami
Emi Hirano
Seiji P Yamamoto
Mitsutoshi Yoneyama
Hiroki Kato
Takashi Fujita
author_sort Ryo Narita
collection DOAJ
description 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.
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spelling doaj.art-6d58c480e109408b8f3a596e4b84af2b2022-12-22T03:42:50ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742014-10-011010e100441710.1371/journal.ppat.1004417A novel function of human Pumilio proteins in cytoplasmic sensing of viral infection.Ryo NaritaKiyohiro TakahasiEtsu MurakamiEmi HiranoSeiji P YamamotoMitsutoshi YoneyamaHiroki KatoTakashi FujitaRIG-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.http://europepmc.org/articles/PMC4207803?pdf=render
spellingShingle Ryo Narita
Kiyohiro Takahasi
Etsu Murakami
Emi Hirano
Seiji P Yamamoto
Mitsutoshi Yoneyama
Hiroki Kato
Takashi Fujita
A novel function of human Pumilio proteins in cytoplasmic sensing of viral infection.
PLoS Pathogens
title A novel function of human Pumilio proteins in cytoplasmic sensing of viral infection.
title_full A novel function of human Pumilio proteins in cytoplasmic sensing of viral infection.
title_fullStr A novel function of human Pumilio proteins in cytoplasmic sensing of viral infection.
title_full_unstemmed A novel function of human Pumilio proteins in cytoplasmic sensing of viral infection.
title_short A novel function of human Pumilio proteins in cytoplasmic sensing of viral infection.
title_sort novel function of human pumilio proteins in cytoplasmic sensing of viral infection
url http://europepmc.org/articles/PMC4207803?pdf=render
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