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

• Main Authors: Jeroen Witteveldt, Alasdair Ivens, Sara Macias
• Format: Article
• Language: English
• Published: Elsevier 2018-06-01
• Series: Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124718307952

Summary: 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. : In order to survive viral infections, cells activate the expression of antiviral cytokines such as IFN-β. Witteveldt et al. show that this response alters the production of miRNAs by regulating the Microprocessor complex and that this regulation is necessary for the robust production of IFN-β. Keywords: microRNAs, microprocessor, DGCR8, Drosha, type I interferon, dsRNA, antiviral