Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-30457
PROVIDER: PRJNA143545 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Dissecting primary (translation independent) from secondary (translation dependent) IFN-mediated differential gene expression
2015-07-07 | E-GEOD-30457 | ExpressionAtlas
Project description:NIH-3T3 cells were pretreated for 15 min with either DMSO (mock) or cycloheximide followed by addition of either mock, 100 U/ml IFNalpha or 100 U/ml IFNgamma for 1h. During the last 30 min, 500 µM 4-thiouridine was added to cell culture medium. Total cellular RNA was isolated using Trizol reagent and nascent RNA was purified as described (Dölken et al. RNA 2008) . Three replicates of nascent RNA were analyzed by Affymetrix Mouse Gene ST 1.0 arrays Primary (translation independent) from secondary (translation dependent) IFN-mediated differential gene expression were studied in NIH-3T3 fibroblasts by studying studying differential gene expression in presence and absence of Cycloheximide (CHX). In addition, the effect of 75 min CHX during the last 30 min of treatment was studied in nascent RNA.
2013-07-04 | E-GEOD-30457 | biostudies-arrayexpress
Project description:IRF1 regulates IFN dependent and independent gene expression
| PRJNA470803 | ENA
Project description:Numerous microRNAs and their target mRNAs are co-expressed across diverse cell types. However, it is unknown whether they are regulated in a cellular context-independent or -dependent manner. Here, we explored transcriptome-wide targeting and gene regulation by miR-155, whose activation-induced expression plays important roles in innate and adaptive immunity. Through mapping of miR-155 targets using differential Argonaute iCLIP, mRNA quantification with RNA-Seq, and 3’UTR usage analysis using polyadenylation (polyA)-Seq in activated miR-155-sufficient and deficient macrophages, dendritic cells, T and B lymphocytes, we identified numerous targets differentially bound by miR-155. While alternative cleavage and polyadenylation (ApA) contributed to differential miR-155 binding to some transcripts, in a majority of cases identical 3’UTR isoforms were differentially regulated across cell types, suggesting ApA-independent and cellular context-dependent miR-155-mediated gene regulation reminiscent of sequence-specific transcription factors. Our study provides comprehensive maps of miR-155 regulatory RNA networks and offers a valuable resource for dissecting context-dependent and -independent miRNA-mediated gene regulation in key cell types of the adaptive and innate immune systems.
2018-06-28 | GSE116348 | GEO
Project description:Numerous microRNAs and their target mRNAs are co-expressed across diverse cell types. However, it is unknown whether they are regulated in a cellular context-independent or -dependent manner. Here, we explored transcriptome-wide targeting and gene regulation by miR-155, whose activation-induced expression plays important roles in innate and adaptive immunity. Through mapping of miR-155 targets using differential Argonaute iCLIP, mRNA quantification with RNA-Seq, and 3’UTR usage analysis using polyadenylation (polyA)-Seq in activated miR-155-sufficient and deficient macrophages, dendritic cells, T and B lymphocytes, we identified numerous targets differentially bound by miR-155. While alternative cleavage and polyadenylation (ApA) contributed to differential miR-155 binding to some transcripts, in a majority of cases identical 3’UTR isoforms were differentially regulated across cell types, suggesting ApA-independent and cellular context-dependent miR-155-mediated gene regulation reminiscent of sequence-specific transcription factors. Our study provides comprehensive maps of miR-155 regulatory RNA networks and offers a valuable resource for dissecting context-dependent and -independent miRNA-mediated gene regulation in key cell types of the adaptive and innate immune systems.
2018-07-02 | GSE116466 | GEO
Project description:Numerous microRNAs and their target mRNAs are co-expressed across diverse cell types. However, it is unknown whether they are regulated in a cellular context-independent or -dependent manner. Here, we explored transcriptome-wide targeting and gene regulation by miR-155, whose activation-induced expression plays important roles in innate and adaptive immunity. Through mapping of miR-155 targets using differential Argonaute iCLIP, mRNA quantification with RNA-Seq, and 3’UTR usage analysis using polyadenylation (polyA)-Seq in activated miR-155-sufficient and deficient macrophages, dendritic cells, T and B lymphocytes, we identified numerous targets differentially bound by miR-155. While alternative cleavage and polyadenylation (ApA) contributed to differential miR-155 binding to some transcripts, in a majority of cases identical 3’UTR isoforms were differentially regulated across cell types, suggesting ApA-independent and cellular context-dependent miR-155-mediated gene regulation reminiscent of sequence-specific transcription factors. Our study provides comprehensive maps of miR-155 regulatory RNA networks and offers a valuable resource for dissecting context-dependent and -independent miRNA-mediated gene regulation in key cell types of the adaptive and innate immune systems.
2018-07-02 | GSE116468 | GEO
Project description:Rocaglamide A (RocA) typifies a class of protein synthesis inhibitors that selectively kill aneuploid tumor cells and repress translation of specific mRNAs. RocA targets eukaryotic initiation factor 4A (eIF4A), an ATP-dependent DEAD-box RNA helicase; its mRNA selectivity is proposed to reflect highly structured 5â² UTRs that depend strongly on eIF4A-mediated unwinding. However, rocaglate treatment may not phenocopy the loss of eIF4A activity, as these drugs actually increase the affinity between eIF4A and RNA. Here, we show that secondary structure in 5â² UTRs is only a minor determinant for RocA selectivity and RocA does not repress translation by reducing eIF4A availability. Rather, in vitro and in cells, RocA specifically clamps eIF4A onto polypurine sequences in an ATP-independent manner. This artificially clamped eIF4A blocks 43S scanning, leading to premature, upstream translation initiation and reducing protein expression from transcripts bearing the RocA-eIF4A target sequence. In elucidating the mechanism of selective translation repression by this lead anti-cancer compound, we provide an example of a drug stabilizing sequence-selective RNA-protein interactions. Bind-n-Seq and iCLIP-Seq
2016-06-15 | E-GEOD-79392 | biostudies-arrayexpress
Project description:In this study we investigated the mechanisms involved in memory T-cell mediated protection using mice vaccinated with the intracellular bacterium Listeria monocytogenes. Our working hypothesis was that rapid activation of cells of the innate immune system, in particular inflammatory Ly6C+ monocytes, were essential in effective protection, in a memory T cell-dependent manner. Thus we generated a comprehensive comparison of the genetic program of activated Ly6C+ monocytes during a primary or a secondary infection with Listeria monocytogenes, at 8 hours post challenge infection. Abstract of corresponding publication: Cells of the innate immune system are essential for host defenses against primary microbial pathogen infections, yet their involvement in effective memory responses of vaccinated individuals has been poorly investigated. Here we show that memory T cells instruct innate cells to become potent effector cells in a systemic and a mucosal model of infection. Memory T cells controlled phagocyte, dendritic cell and NK or NK T cell mobilization and induction of a strong program of differentiation, which included their expression of effector cytokines and microbicidal pathways, all of which were delayed in non-vaccinated hosts. Disruption of IFN-gamma-signaling in Ly6C+ monocytes, dendritic cells and macrophages impaired these processes and the control of pathogen growth. These results reveal how memory T cells, through rapid secretion of IFN-gamma, orchestrate extensive modifications of host innate immune responses that are essential for effective protection of vaccinated hosts. Overall design: Inflammatory monocytes were purified (see below for isolation method) from 4 groups of 3 individual mice each (triplicate): (i) uninfected mice, (ii) primary infected, (iii) secondary infected, (iv) secondary infected and T-cell depleted 1 day before. Isolation of cells was done on 3 different days for true biological replicates.
2015-06-04 | E-GEOD-58014 | biostudies-arrayexpress
Project description:IFN-g primes macrophages for enhanced inflammatory activation by TLRs and microbial killing, but little is known about the regulation of cell metabolism or mRNA translation during priming. We found that IFN-g regulates macrophage metabolism and translation in an integrated manner by targeting mTORC1 and MNK pathways that converge on the selective regulator of translation initiation eIF4E. Physiological downregulation of the central metabolic regulator mTORC1 by IFN-g was associated with autophagy and translational suppression of repressors of inflammation such as HES1. Genome-wide ribosome profiling in TLR2-stimulated macrophages revealed that IFN-g selectively modulates the macrophage translatome to promote inflammation, further reprogram metabolic pathways, and modulate protein synthesis. These results add IFN-g-mediated metabolic reprogramming and translational regulation as key components of classical inflammatory macrophage activation. RPF and RNAseq libraries were generated from mock or IFN-g-primed human macrophages. Cells were stimulated with Pam3Cys and harvested at 4 hours. Libraries were generated using protocol modified from Illumina Truseq technology.
2015-06-29 | E-GEOD-66809 | biostudies-arrayexpress
Project description:IFN-g primes macrophages for enhanced inflammatory activation by TLRs and microbial killing, but little is known about the regulation of cell metabolism or mRNA translation during priming. We found that IFN-g regulates macrophage metabolism and translation in an integrated manner by targeting mTORC1 and MNK pathways that converge on the selective regulator of translation initiation eIF4E. Physiological downregulation of the central metabolic regulator mTORC1 by IFN-g was associated with autophagy and translational suppression of repressors of inflammation such as HES1. Genome-wide ribosome profiling in TLR2-stimulated macrophages revealed that IFN-g selectively modulates the macrophage translatome to promote inflammation, further reprogram metabolic pathways, and modulate protein synthesis. These results add IFN-g-mediated metabolic reprogramming and translational regulation as key components of classical inflammatory macrophage activation. microRNA-seq libraries were generated from mock or IFN-g-primed human macrophages. Cells were stimulated with or without Pam3Cys and harvested at 4 hours Libraries were generated using Illumina Truseq small RNA technology.
2015-06-29 | E-GEOD-66808 | biostudies-arrayexpress