Project description:The type I interferon (IFN-I) response shapes the intracellular environment to supress virus infection. Historically, this remodelling has been linked to the transcriptional induction of interferon stimulated genes (ISGs). However, IFN-I-driven post-translational regulation of proteins already present in the cell remains relatively unexplored. Here, we profiled the activity of cellular RNA-binding proteins (RBPs), which are key players in antiviral immunity. Using RNA interactome capture (RIC), we identified hundreds of RBPs whose association with RNA is regulated by IFN-I (IR-RBPs). Among these IR-RBPs are both known antiviral proteins and novel candidates identified here through a knockdown screen. By modifying RIC to study IR-RBPs' phosphorylation states, we identified several putative instances of IFN-I-driven phospho-regulation of RNA binding. We experimentally confirmed this phospho-driven regulation for MATR3. Altogether, our results reveal a new dimension of the cell’s antiviral programme, in which the cellular RNA-bound proteome is remodelled by IFN-I.
Project description:Human neuronal differentiation alters responsiveness to innate immune stimuli and virus infections. We used microarrays to examine the transcriptional responses of the human BE(2)-C neuroblastoma cell line to retinoic acid-induced differentiation and type I IFN stimulation.
Project description:The type I interferon (IFN-I) response shapes the intracellular environment to supress virus infection. Historically, this remodelling has been linked to the transcriptional induction of interferon stimulated genes (ISGs). However, whether IFN-I alters the activity of proteins already present in the cell remains largely unexplored. Here, we profiled the activity of cellular RNA-binding proteins (RBPs), which are key players in antiviral immunity. Using RNA interactome capture (RIC), we identified hundreds of RBPs whose association with RNA is regulated by IFN-I (IR-RBPs). Among these IR-RBPs are known antiviral proteins, as well as novel antiviral candidates, identified through functional assays. By modifying RIC to study IR-RBPs' phosphorylation states, we identified several putative instances of IFN-I-driven phospho-regulation of RNA binding. We experimentally confirmed that MATR3’s IFN-regulated S188 phosphosite modulates its RNA-binding activity, speaking to an exciting new layer of regulation. Altogether, our results reveal a new dimension of the cell’s antiviral programme, in which the cellular RNA-bound proteome is remodelled by IFN-I.
Project description:TruCulture human whole blood ex vivo stimulation was performed on 17 healthy individuals and 17 post-onset type 1 diabetics, then gene expression was analyzed using Nanostring to characterize stimulated innate immune responses. Ex vivo whole blood stimulation revealed higher induced IFN-1 responses in type 1 diabetes as compared to healthy controls.
Project description:Human neuronal differentiation alters responsiveness to innate immune stimuli and virus infections. We used microarrays to examine the transcriptional responses of the human BE(2)-C neuroblastoma cell line to retinoic acid-induced differentiation and type I IFN stimulation. Experiment Overall Design: Cultured BE(2)-C cells were differentiated with 10 uM all-trans retinoic acid (RA) for 3 weeks, incubated with universal type I IFN (IFNa-A/D) for 6 or 12 h, and Affymetrix Human Genome Array U133 Plus 2.0 chips were used to analyze transcript levels.
Project description:This SuperSeries is composed of the following subset Series:; GSE16450: Human BE(2)-C neuronal responses to type I IFN stimulation; GSE16451: Human BE(2)-C neuronal responses to WEEV infection Experiment Overall Design: Refer to individual Series