3' UTR RNA-sequencing of human lung adenocarcinoma cell lines PC9 and A549 treated with RIG-I agonist IVT4/unspecific control IVT-GAC
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina NovaSeq 6000
ORGANISM(S): Homo sapiens
SUBMITTER: Johannes Braegelmann
PROVIDER: E-MTAB-10802 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Immunocompromised mice were inoculated with human lung adenocarcinoma cell line PC9 and with human PBMCs. Tumors were treated with osimertinib/vehicle of RIG-I agonist IVT4/unspecific control IVT-GAC to assess response.
2021-07-20 | E-MTAB-9891 | biostudies-arrayexpress
Project description:3' UTR RNA-sequencing of human lung adenocarcinoma cell lines PC9 and A549 treated with RIG-I agonist IVT4/unspecific control IVT-GAC
| PRJEB46744 | ENA
Project description:3' UTR RNA-sequencing of humanized EGFR-mutant PC9 cell line xenografts treated with osimertinib/vehicle of RIG-I agonist IVT4/unspecific control IVT-GAC
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Project description:The RIG-I like receptor pathway is stimulated during RNA virus infection by interaction between cytosolic RIG-I and viral RNA structures that contain short hairpin dsRNA and 5M-bM-^@M-^Y triphosphate (5M-bM-^@M-^Yppp) terminal structure. In the present study, an RNA agonist of RIG-I was synthesized in vitro and shown to stimulate RIG-I-dependent antiviral responses at concentrations in the picomolar range. In human lung epithelial A549 cells, 5M-bM-^@M-^YpppRNA specifically stimulated multiple parameters of the innate antiviral response, including IRF3, IRF7 and STAT1 activation, andinduction of inflammatory and interferon stimulated genes - hallmarks of a fully functional antiviral response. Evaluation of the magnitude and duration of gene expression by transcriptional profiling identified a robust, sustained and diversified antiviral and inflammatory response characterized by enhanced pathogen recognition and interferon (IFN)signaling. Bioinformatics analysis further identified a transcriptional signature uniquely induced by 5M-bM-^@M-^YpppRNA, and not by IFNM-NM-1-2bthat included a constellation of IRF7 and NF-kB target genes capable of mobilizing multiple arms of the innate and adaptive immune response. Treatment of primary PBMCs or lung epithelial A549 cells with 5M-bM-^@M-^YpppRNA provided significant protection against a spectrum of RNA and DNA viruses. In C57Bl/6 mice, intravenous administration of 5M-bM-^@M-^YpppRNA protected animals from a lethal challenge with H1N1 Influenza, reduced virus titers in mouse lungs and protected animals from virus-induced pneumonia. Strikingly, the RIG-I-specific transcriptional response afforded partial protection from influenza challenge, even in the absence of type I interferon signaling. This systems approach providestranscriptional, biochemical, and in vivo analysis of the antiviral efficacy of 5M-bM-^@M-^YpppRNA and highlights the therapeutic potential associated with the use of RIG-I agonists as broad spectrum antiviral agents. Kinetic analysis of A549 cells treated with 5'pppRNA and analyzed at 1h, 2h, 4h, 6h, 8h, 12h, 24h or 48h.
2014-08-21 | E-GEOD-60573 | biostudies-arrayexpress
Project description:The RIG-I like receptor pathway is stimulated during RNA virus infection by interaction between cytosolic RIG-I and viral RNA structures that contain short hairpin dsRNA and 5M-bM-^@M-^Y triphosphate (5M-bM-^@M-^Yppp) terminal structure. In the present study, an RNA agonist of RIG-I was synthesized in vitro and shown to stimulate RIG-I-dependent antiviral responses at concentrations in the picomolar range. In human lung epithelial A549 cells, 5M-bM-^@M-^YpppRNA specifically stimulated multiple parameters of the innate antiviral response, including IRF3, IRF7 and STAT1 activation, andinduction of inflammatory and interferon stimulated genes - hallmarks of a fully functional antiviral response. Evaluation of the magnitude and duration of gene expression by transcriptional profiling identified a robust, sustained and diversified antiviral and inflammatory response characterized by enhanced pathogen recognition and interferon (IFN)signaling. Bioinformatics analysis further identified a transcriptional signature uniquely induced by 5M-bM-^@M-^YpppRNA, and not by IFNM-NM-1-2bthat included a constellation of IRF7 and NF-kB target genes capable of mobilizing multiple arms of the innate and adaptive immune response. Treatment of primary PBMCs or lung epithelial A549 cells with 5M-bM-^@M-^YpppRNA provided significant protection against a spectrum of RNA and DNA viruses. In C57Bl/6 mice, intravenous administration of 5M-bM-^@M-^YpppRNA protected animals from a lethal challenge with H1N1 Influenza, reduced virus titers in mouse lungs and protected animals from virus-induced pneumonia. Strikingly, the RIG-I-specific transcriptional response afforded partial protection from influenza challenge, even in the absence of type I interferon signaling. This systems approach providestranscriptional, biochemical, and in vivo analysis of the antiviral efficacy of 5M-bM-^@M-^YpppRNA and highlights the therapeutic potential associated with the use of RIG-I agonists as broad spectrum antiviral agents. A549 cells were either non-treated, treated with RNAiMax only, transfected with 5'pppRNA, or treated with IFNa-2b and analysed at 6h or 24h.
2014-08-21 | E-GEOD-60572 | biostudies-arrayexpress
Project description:We identified a small molecule compound, KIN1148, that directly binds RIG-I to drive IRF3 and NF B activation and expression of innate immune genes, cytokines and chemokines. KIN1148 activates RIG-I in an RNA- and ATP-independent manner and does not induce a canonical antiviral interferon (IFN) gene program traditionally associated with RIG-I activation. When administered in combination with a vaccine against influenza A virus (IAV), KIN1148 induces both neutralizing antibody and broadly cross-protective IAV-specific T cell responses compared to vaccination alone, which induces poor responses. In this study, we demonstrate that KIN1148 directly engages RIG-I to activate IRF3- and NFB-dependent innate immune responses, making it the first small molecule RIG-I agonist to be identified. Biochemical studies show that KIN1148 binds to RIG-I to drive RIG-I self-oligomerization and downstream signaling activation in an RNA- and ATP-independent manner. We further find that transcriptional programs induced by KIN1148 treatment exhibit shared and unique signatures to that induced by other methods of RIG-I activation, including Sendai virus (SeV) infection and PAMP RNA transfection. KIN1148 adjuvants a split virus (SV) vaccine at suboptimal dose to protect mice from lethal challenge with a recombinant highly pathogenic avian H5N1 influenza virus, A/Vietnam/1203/2004.
2022-06-14 | GSE205964 | GEO
Project description:We identified SMYD5 (SET and MYND Domain-Containing Protein 5) physiologically methylates core ribosomal protein L40 at lysine 22 (rpL40K22me3).In mouse GAC model, we observed rpL40K22me3 stoichiometry is saturating in both normal and GAC tissue.
2024-06-04 | PXD052359 | Pride
Project description:We performed RNAseq analysis on WT and LGP2-/- BM-DCs treated with a RIG-I agonist (HCV Poly-U/C RNA) to understand how LGP2 impacts global transcriptional changes following activation of the RIG-I pathway. Analysis of the transcriptional profiles revealed that LGP2 functions as a negative regulator of RIG-I signaling as early as 1 hours post-RIG-I agonist treatment. This finding led us to study how LGP2 negatively influences RIG-I activation through post-translational modification.
2019-06-14 | GSE132696 | GEO
Project description:The gene GLS generates the phosphate activated glutaminase C (GAC) isoform by alternative splicing. GAC, compared to the other isoform, kidney-type glutaminase (KGA), has been characterized as more active and particularly important for cancer cell growth. Very little is known about post-translational modifications regulating GAC function. Hereby we describe the identification of a phosphorylation on the serine 95, located at the GLS N-terminus, a domain shared by both isoforms. A GAC phosphomimetic mutant (S95D) ectopically expressed in breast cancer cells presented decreased enzymatic activity, and its expression impacted on cell’s glutamine uptake, glutamate release and intracellular glutamate levels (compared to expressing wild type GAC) without changing GAC sub-cellular localization. Curiously, replacing S95 by an alanine in the ectopically expressed GAC (S95A) increased cell proliferation and migration. Taken together, these results reveal that GAC is post-translationally regulated by phosphorylation, which impacts on cancer phenotype.
2018-08-13 | PXD008338 | Pride
Project description:The RIG-I like receptor pathway is stimulated during RNA virus infection by interaction between cytosolic RIG-I and viral RNA structures that contain short hairpin dsRNA and 5’ triphosphate (5’ppp) terminal structure. In the present study, an RNA agonist of RIG-I was synthesized in vitro and shown to stimulate RIG-I-dependent antiviral responses at concentrations in the picomolar range. In human lung epithelial A549 cells, 5’pppRNA specifically stimulated multiple parameters of the innate antiviral response, including IRF3, IRF7 and STAT1 activation, andinduction of inflammatory and interferon stimulated genes - hallmarks of a fully functional antiviral response. Evaluation of the magnitude and duration of gene expression by transcriptional profiling identified a robust, sustained and diversified antiviral and inflammatory response characterized by enhanced pathogen recognition and interferon (IFN)signaling. Bioinformatics analysis further identified a transcriptional signature uniquely induced by 5’pppRNA, and not by IFNα-2bthat included a constellation of IRF7 and NF-kB target genes capable of mobilizing multiple arms of the innate and adaptive immune response. Treatment of primary PBMCs or lung epithelial A549 cells with 5’pppRNA provided significant protection against a spectrum of RNA and DNA viruses. In C57Bl/6 mice, intravenous administration of 5’pppRNA protected animals from a lethal challenge with H1N1 Influenza, reduced virus titers in mouse lungs and protected animals from virus-induced pneumonia. Strikingly, the RIG-I-specific transcriptional response afforded partial protection from influenza challenge, even in the absence of type I interferon signaling. This systems approach providestranscriptional, biochemical, and in vivo analysis of the antiviral efficacy of 5’pppRNA and highlights the therapeutic potential associated with the use of RIG-I agonists as broad spectrum antiviral agents.
2014-08-21 | GSE60573 | GEO