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Inhibition of Microprocessor Function during the Activation of the Type I Interferon Response

Type I interferons (IFNs) are central components of the antiviral response. Most cell types respond to viral infections by secreting IFNs, but the mechanisms that regulate correct expression of these cytokines are not completely understood. Here, we show that activation of the type I IFN response re...

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Detalles Bibliográficos
Autores principales: Witteveldt, Jeroen, Ivens, Alasdair, Macias, Sara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019736/
https://www.ncbi.nlm.nih.gov/pubmed/29898398
http://dx.doi.org/10.1016/j.celrep.2018.05.049
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author Witteveldt, Jeroen
Ivens, Alasdair
Macias, Sara
author_facet Witteveldt, Jeroen
Ivens, Alasdair
Macias, Sara
author_sort Witteveldt, Jeroen
collection PubMed
description Type I interferons (IFNs) are central components of the antiviral response. Most cell types respond to viral infections by secreting IFNs, but the mechanisms that regulate correct expression of these cytokines are not completely understood. Here, we show that activation of the type I IFN response regulates the expression of miRNAs in a post-transcriptional manner. Activation of IFN expression alters the binding of the Microprocessor complex to pri-miRNAs, reducing its processing rate and thus leading to decreased levels of a subset of mature miRNAs in an IRF3-dependent manner. The rescue of Microprocessor function during the antiviral response downregulates the levels of IFN-β and IFN-stimulated genes. All these findings support a model by which the inhibition of Microprocessor activity is an essential step to induce a robust type I IFN response in mammalian cells.
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spelling pubmed-60197362018-06-28 Inhibition of Microprocessor Function during the Activation of the Type I Interferon Response Witteveldt, Jeroen Ivens, Alasdair Macias, Sara Cell Rep Article Type I interferons (IFNs) are central components of the antiviral response. Most cell types respond to viral infections by secreting IFNs, but the mechanisms that regulate correct expression of these cytokines are not completely understood. Here, we show that activation of the type I IFN response regulates the expression of miRNAs in a post-transcriptional manner. Activation of IFN expression alters the binding of the Microprocessor complex to pri-miRNAs, reducing its processing rate and thus leading to decreased levels of a subset of mature miRNAs in an IRF3-dependent manner. The rescue of Microprocessor function during the antiviral response downregulates the levels of IFN-β and IFN-stimulated genes. All these findings support a model by which the inhibition of Microprocessor activity is an essential step to induce a robust type I IFN response in mammalian cells. Cell Press 2018-06-13 /pmc/articles/PMC6019736/ /pubmed/29898398 http://dx.doi.org/10.1016/j.celrep.2018.05.049 Text en © 2018 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Witteveldt, Jeroen
Ivens, Alasdair
Macias, Sara
Inhibition of Microprocessor Function during the Activation of the Type I Interferon Response
title Inhibition of Microprocessor Function during the Activation of the Type I Interferon Response
title_full Inhibition of Microprocessor Function during the Activation of the Type I Interferon Response
title_fullStr Inhibition of Microprocessor Function during the Activation of the Type I Interferon Response
title_full_unstemmed Inhibition of Microprocessor Function during the Activation of the Type I Interferon Response
title_short Inhibition of Microprocessor Function during the Activation of the Type I Interferon Response
title_sort inhibition of microprocessor function during the activation of the type i interferon response
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6019736/
https://www.ncbi.nlm.nih.gov/pubmed/29898398
http://dx.doi.org/10.1016/j.celrep.2018.05.049
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