Translational control of the activation of transcription factor NF-?B and production of type I interferon by phosphorylation of the translation factor eIF4E

Barbara Herdy, Martiza Jaramillo, Yuri V Svitkin, Amy B Rosenfeld, Mariko Kobayashi, Derek Walsh, Tommy Alain, Polen Sean, Nathaniel Robichaud, Ivan Topisirovic, Luc Furic, Ryan J O Dowling, Annie Sylvestre, Liwei Rong, Rodney Colina, Mauro Costa-Mattioli, Jorg H Fritz, Martin Olivier, Earl Brown, Ian MohrNahum Sonenberg

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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 IkappaBalpha), largely explained this phenotype. The lower abundance of IkappaBalpha resulted in enhanced activity of the transcription factor NF-kappaB, which promoted the production of interferon-beta (IFN-beta). 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.
Original languageEnglish
Pages (from-to)543 - 550
Number of pages8
JournalNature Immunology
Volume13
Issue number6
DOIs
Publication statusPublished - 2012

Cite this

Herdy, B., Jaramillo, M., Svitkin, Y. V., Rosenfeld, A. B., Kobayashi, M., Walsh, D., Alain, T., Sean, P., Robichaud, N., Topisirovic, I., Furic, L., Dowling, R. J. O., Sylvestre, A., Rong, L., Colina, R., Costa-Mattioli, M., Fritz, J. H., Olivier, M., Brown, E., ... Sonenberg, N. (2012). Translational control of the activation of transcription factor NF-?B and production of type I interferon by phosphorylation of the translation factor eIF4E. Nature Immunology, 13(6), 543 - 550. https://doi.org/10.1038/ni.2291