LncRNA CARINH regulates expression and function of innate transcription factor IRF1 in macrophages [RNA-Seq 2]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE261123 | GEO | 2025/01/03
REPOSITORIES: GEO
Similar Datasets
Project description:The antisense lncRNA CARINH acts as an additional regulatory layer of antiviral immunity through coordinated regulation of the transcription factor IRF1 and downstream interferon-stimulated genes.
2025-01-03 | GSE247501 | GEO
Project description:Long non-coding RNAs (lncRNAs) are important regulators of the immune response. Here we study lincRNA IRF1-AS1 (human) and its mouse ortholog Gm12216. We established that IRF1-AS1/Gm12216 is involved in the antiviral response.
2025-01-06 | GSE275288 | GEO
Project description:Oncolytic viruses exploit common molecular changes in cancer cells, which are not present in normal cells, to target and kill cancer cells. Ras transformation and defects in type I interferon (IFN)-mediated antiviral responses are known to be the major mechanisms underlying viral oncolysis. Previously, we demonstrated that oncogenic RAS/Mitogen-activated protein kinase kinase (Ras/MEK) activation suppresses the transcription of many IFN-inducible genes in human cancer cells, suggesting that Ras transformation underlies type I IFN defects in cancer cells. Here, we investigated how Ras/MEK downregulates IFN-induced transcription. By conducting promoter deletion analysis of IFN-inducible genes, namely guanylate-binding protein 2 and IFN gamma inducible protein 47 (Ifi47), we identified the IFN regulatory factor 1 (IRF1) binding site as the promoter region responsible for the regulation of transcription by MEK. MEK inhibition promoted transcription of the IFN-inducible genes in wild type mouse embryonic fibroblasts (MEFs), but not in IRF1?/? MEFs, showing that IRF1 is involved in MEK-mediated downregulation of IFN-inducible genes. Furthermore, IRF1 protein expression was lower in RasV12 cells compared with vector control NIH3T3 cells, but was restored to equivalent levels by inhibition of MEK. Similarly, the restoration of IRF1 expression by MEK inhibition was observed in human cancer cells. IRF1 re-expression in human cancer cells caused cells to become resistant to infection by the oncolytic vesicular stomatitis virus strain. Together, this work demonstrates that Ras/MEK activation in cancer cells downregulates transcription of IFN-inducible genes by targeting IRF1 expression, resulting in increased susceptibility to viral oncolysis. RNA was isolated from RasV12 transformed NIH/3T3 cells (RasV12 cells) treated with 20?M U0126 or 500U/ml IFN-?, or left untreated, for 6 hours, triplicate biological samples (9 samples).
2014-11-13 | E-GEOD-49469 | biostudies-arrayexpress
Project description:Inborn errors of human IFN-γ immunity underlie mycobacterial diseases, whereas inborn errors of IFN-a/b immunity underlie viral diseases. Both types of IFNs induce the transcription factor IRF1. We describe two unrelated children with inherited complete IRF1 deficiency and early-onset, multiple, life-threatening diseases caused by weakly virulent mycobacteria. These children have no history of severe viral disease, despite exposure to many viruses, including SARS-CoV-2, which is life-threatening in individuals with impaired IFN-a/b immunity. The IRF1-dependent cellular responses to IFN-γ are, both quantitatively and qualitatively, much greater than those to IFN-a/b in vitro. Monocyte- and iPSC-derived macrophages from the two patients show no upregulation of at least 20% of the target genes normally induced by IFN-γ. By contrast, cell-intrinsic IFN-a/b immunity to diverse viruses, including SARS-CoV-2, is intact. Human IRF1 is, thus, largely redundant for antiviral IFN-a/b immunity. By contrast, human IRF1 is essential for IFN-γ immunity to mycobacteria in myeloid cells.
2023-01-19 | PXD037759 | Pride
Project description:IRF1, and interferon-induced transcription factor, was found to have antiviral activity against a range of viruses when overexpressed. To determine which genes are associated with expression of IRF1, gene expression analysis was carried out in two different cell line expressing IRF1. The results show that more than 100 genes, many of which overlap with type I interferon-stimulated genes, are induced more than 3-fold by IRF1. A majority of the genes were induced in both cell types, while some genes were highly induced in a cell type-specific manner. To investigate the impact of IRF1 overexpression on the transriptome of two target cell lines, cells were transduced with a lentiviral vector expressing IRF1 or Firefly luciferase (Fluc) as a control. Total mRNA was harvested 48 h post-transduction and processed for Illumina BeadArray analysis. Skin fibroblast cell line described in Dupuis, S. et al., Impaired response to interferon-alpha/beta and lethal viral disease in human STAT1 deficiency. Nat Genet 33 (3), 388 (2003)
2011-04-01 | E-GEOD-26817 | biostudies-arrayexpress
Project description:Interferon regulatory factors (IRFs) play key roles in the transactivation of antiviral genes at the step downstream of activated pathogen-associated molecular pattern sensors, such as RIG-I-like receptors or Toll-like receptors. Whereas IRF1 and IRF3 are thought to bind similar DNA elements (ISRE and PRD-III, PRD-I) to activate antiviral gene transcription, genome-wide transcriptome profiling of IRF1 versus IRF3 knockouts in an immortalized primary hepatocyte (PH5CH8) cell line infected with hepatitis A virus (HAV) revealed unexpected disparities in their target genes. IRF1 targets include several anti-HAV effector genes that were not previously recognized to have antiviral functions.
2018-06-01 | GSE114916 | GEO
Project description:LncRNA CARINH regulates expression and function of innate transcription factor IRF1 in macrophages [RNA-Seq]
| PRJNA1039021 | ENA
Project description:LncRNA Hypoxia-inducible factor 1α-antisense 1 (HIF1α-AS1) is located on the antisense strand of the important Hypoxia-inducible factor 1α (HIF1α) gene, but being transcribed in antisense direction along the HIF1α promoter. Here we used the 3’end biotinylated HIF1a-AS1 RNA and a control RNA for RNA Pulldown and searched for interacting proteins in nuclear extracts of human umbilical vein endothelial cells (HUVEC).
2022-09-23 | PXD023512 | Pride
Project description:Inborn errors of human IFN-γ-dependent macrophagic immunity underlie mycobacterial diseases, whereas inborn errors of IFN-α/β-dependent intrinsic immunity underlie viral diseases. Both types of IFNs induce the transcription factor IRF1. We describe unrelated children with inherited complete IRF1 deficiency and early-onset, multiple, life-threatening diseases caused by weakly virulent mycobacteria and related intramacrophagic pathogens. These children have no history of severe viral disease, despite exposure to many viruses, including SARS-CoV-2, which is life-threatening in individuals with impaired IFN-α/β immunity. In leukocytes or fibroblasts stimulated in vitro, IRF1-dependent responses to IFN-γ are, both quantitatively and qualitatively, much stronger than those to IFN-α/β. Moreover, IRF1-deficient mononuclear phagocytes do not control mycobacteria and related pathogens normally when stimulated with IFN-γ. By contrast, IFN-α/β-dependent intrinsic immunity to nine viruses, including SARS-CoV-2, is almost normal in IRF1-deficient fibroblasts. Human IRF1 is essential for IFN-γ-dependent macrophagic immunity to mycobacteria, but largely redundant for IFN-α/β-dependent antiviral immunity.
2023-05-12 | GSE203220 | GEO
Project description:Inborn errors of human IFN-γ immunity underlie mycobacterial diseases, whereas inborn errors of IFN-/ immunity underlie viral diseases. Both types of IFNs induce the transcription factor IRF1. We describe two unrelated children with inherited complete IRF1 deficiency and early-onset, multiple, life-threatening diseases caused by weakly virulent mycobacteria. These children have no history of severe viral disease, despite exposure to many viruses, including SARS-CoV-2, which is life-threatening in individuals with impaired IFN-/ immunity. The IRF1-dependent cellular responses to IFN-γ are, both quantitatively and qualitatively, much greater than those to IFN-/ in vitro. Monocyte- and iPSC-derived macrophages from the two patients show no upregulation of at least 20% of the target genes normally induced by IFN-γ. By contrast, cell-intrinsic IFN-/ immunity to diverse viruses, including SARS-CoV-2, is intact. Human IRF1 is, thus, largely redundant for antiviral IFN-/ immunity. By contrast, human IRF1 is essential for IFN-γ immunity to mycobacteria in myeloid cells.
2023-01-12 | GSE218033 | GEO