title: Translational control of the activation of transcription factor NF-κB and production of type I interferon by phosphorylation of the translation factor eIF4E.
abstract: Type I interferon is an integral component of the antiviral response, and its production is tightly controlled at the levels of transcription and translation. The eukaryotic translation-initiation factor eIF4E is a rate-limiting factor whose activity is regulated by phosphorylation of Ser209. Here we found that mice and fibroblasts in which eIF4E cannot be phosphorylated were less susceptible to virus infection. More production of type I interferon, resulting from less translation of Nfkbia mRNA (which encodes the inhibitor IκBα), largely explained this phenotype. The lower abundance of IκBα resulted in enhanced activity of the transcription factor NF-κB, which promoted the production of interferon-β (IFN-β). Thus, regulated phosphorylation of eIF4E has a key role in antiviral host defense by selectively controlling the translation of an mRNA that encodes a critical suppressor of the innate antiviral response.
authors.affiliation: Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: Barbara
authors.initials: B
authors.lastname: Herdy
authors.affiliation: Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: Maritza
authors.initials: M
authors.lastname: Jaramillo
authors.affiliation: Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: Yuri V
authors.initials: YV
authors.lastname: Svitkin
authors.affiliation: Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: Amy B
authors.initials: AB
authors.lastname: Rosenfeld
authors.affiliation: Department of Microbiology and NYU Cancer Institute, New York University School of Medicine, New York, New York, USA.
authors.forename: Mariko
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.
authors.forename: Derek
authors.initials: D
authors.lastname: Walsh
authors.affiliation: Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: Tommy
authors.initials: T
authors.lastname: Alain
authors.affiliation: Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: Polen
authors.initials: P
authors.lastname: Sean
authors.affiliation: Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Robichaud
authors.affiliation: Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: Ivan
authors.initials: I
authors.lastname: Topisirovic
authors.affiliation: Monash University, Clayton, Australia.
authors.forename: Luc
authors.initials: L
authors.lastname: Furic
authors.affiliation: Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: Ryan J O
authors.initials: RJO
authors.lastname: Dowling
authors.affiliation: Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: Annie
authors.initials: A
authors.lastname: Sylvestre
authors.affiliation: McGill AIDS Center, Lady Davis Institute of the Jewish General Hospital, Montreal, Canada.
authors.forename: Liwei
authors.initials: L
authors.lastname: Rong
authors.affiliation: Laboratorio de Virologia Molecular, Regional Norte-Salto, Universidad de la República, Salto, Uruguay.
authors.forename: Rodney
authors.initials: R
authors.lastname: Colina
authors.affiliation: Department of Neuroscience, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Mauro
authors.initials: M
authors.lastname: Costa-Mattioli
authors.affiliation: Complex Traits Group and Department of Microbiology and Immunology, McGill University, Montreal, Canada.
authors.forename: Jörg H
authors.initials: JH
authors.lastname: Fritz
authors.affiliation: The Research Institute of the McGill University Health Centre, Centre for the Study of Host Resistance, Departments of Medicine, Microbiology and Immunology, McGill University, Montreal, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Olivier
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, and Emerging Pathogens Research Centre, University of Ottawa, Ottawa, Canada.
authors.forename: Earl
authors.initials: E
authors.lastname: Brown
authors.affiliation: Department of Microbiology and NYU Cancer Institute, New York University School of Medicine, New York, New York, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Mohr
authors.affiliation: Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: Nahum
authors.initials: N
authors.lastname: Sonenberg
mesh_terms: D000818:Animals; D024202:Electrophoretic Mobility Shift Assay; D039561:Eukaryotic Initiation Factor-4E / Q000276:immunology / Q000378:metabolism*; D005260:Female; D020672:I-kappa B Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology; D015151:Immunoblotting; D007370:Interferon Type I / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D054243:Vesicular Stomatitis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology / Q000502:physiology*; D014779:Virus Replication
chemical_list: D039561:Eukaryotic Initiation Factor-4E; D020672:I-kappa B Proteins; D007370:Interferon Type I; D016328:NF-kappa B; C000606205:Nfkbia protein, mouse; D012333:RNA, Messenger; D000072000:NF-KappaB Inhibitor alpha