Human DICER helicase domain recruits PKR and modulates its antiviral activity
| Autor: | Philippe Hammann, Sébastien Pfeffer, Mathieu Lefèvre, Erika Girardi, Johana Chicher, Morgane Baldaccini, Mélanie Messmer, Thomas Montavon, Béatrice Chane-Woon-Ming |
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| Přispěvatelé: | Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), univOAK, Archive ouverte |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Ribonuclease III
Small interfering RNA Physiology viruses Interaction Networks RNA-binding protein Virus Replication Biochemistry DEAD-box RNA Helicases eIF-2 Kinase RNA interference 0302 clinical medicine Interferon Immune Physiology Medicine and Health Sciences Biology (General) 0303 health sciences Immune System Proteins biology 030302 biochemistry & molecular biology food and beverages RNA Helicase A Enzymes Precipitation Techniques 3. Good health Cell biology Nucleic acids RNA silencing Genetic interference Interferon Type I Helicases Epigenetics Research Article medicine.drug QH301-705.5 Immunology Research and Analysis Methods Transfection Antiviral Agents Microbiology Antibodies 03 medical and health sciences Virology [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology Genetics medicine Humans Immunoprecipitation Protein Interaction Domains and Motifs [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Non-coding RNA Molecular Biology Techniques Molecular Biology 030304 developmental biology Alphavirus Infections fungi Biology and Life Sciences Proteins Helicase RC581-607 Semliki forest virus Protein kinase R Gene regulation enzymes and coenzymes (carbohydrates) HEK293 Cells Enzymology biology.protein RNA Parasitology Gene expression Immunologic diseases. Allergy 030217 neurology & neurosurgery Cloning Dicer |
| Zdroj: | PLoS Pathogens PLoS Pathogens, Public Library of Science, 2021, 17 (5), pp.e1009549. ⟨10.1371/journal.ppat.1009549⟩ PLOS Pathogens bioRxiv PLoS Pathogens, 2021, 17 (5), pp.e1009549. ⟨10.1371/journal.ppat.1009549⟩ PLoS Pathogens, Vol 17, Iss 5, p e1009549 (2021) |
| ISSN: | 1553-7366 1553-7374 |
| Popis: | The antiviral innate immune response mainly involves type I interferon (IFN) in mammalian cells. The contribution of the RNA silencing machinery remains to be established, but several recent studies indicate that the ribonuclease DICER can generate viral siRNAs in specific conditions. It has also been proposed that type I IFN and RNA silencing could be mutually exclusive antiviral responses. In order to decipher the implication of DICER during infection of human cells with alphaviruses such as the Sindbis virus and Semliki forest virus, we determined its interactome by proteomics analysis. We show that DICER specifically interacts with several double-stranded RNA binding proteins and RNA helicases during viral infection. In particular, proteins such as DHX9, ADAR-1 and the protein kinase RNA-activated (PKR) are enriched with DICER in virus-infected cells. We demonstrate that the helicase domain of DICER is essential for this interaction and that its deletion confers antiviral properties to this protein in an RNAi-independent, PKR-dependent, manner. Author summary While RNAi has been recognized as an efficient antiviral defense system in organisms such as plants and insects, its physiological importance in mammals remains to be determined. DICER is an enzyme involved in cleaving long double-stranded RNAs and is essential for RNAi induction. Using mass spectrometry analysis, we determined its interactome in human cells and showed that RNA binding proteins such as PKR are specifically enriched upon infection with the Sindbis virus or the Semliki forest virus. We determined that the N terminal helicase domain of the DICER protein acts as a platform to recruit these factors during infection and that its deletion confers an antiviral activity to DICER. |
| Databáze: | OpenAIRE |
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