Alternate isoforms of IRF7 Differentially Regulate Interferon Expression
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1203213 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Interferon Regulatory Factor 7 (IRF7), and its homologue IRF3, are master transcriptional regulators of the innate immune response. IRF7 binds to promoters of interferon beta (IFNb) and several IFNas, as a homodimer or as a heterodimer with IRF3 to drive expression of these type I IFNs, which in turn activate additional signaling pathways to promote expression of anti-viral genes. Here we demonstrate that retention of the first intron within the coding region of IRF7 is highly regulated across immune tissues and in response to viral infection and other immunologic signals. Importantly, retention of this intron generates an alternative translation start site, resulting in a N-terminally extended form of the protein (exIRF7). Using CRISPR gene editing to generate cells that only express exIRF7, or the canonical version of IRF7 (cIRF7), we demonstrate that exIRF7 uniquely activates a program of genes, including IFNb, in response to innate immune triggers. We conclude that alternative splicing of IRF7 is a previously unrecognized mechanisms used by human cells to tune the interferon response to viral infection and other immune challenges.
2025-07-17 | GSE285352 | GEO
Project description:miR-222 isoforms are differentially regulated by type-I interferon
| PRJEB22632 | ENA
Project description:We found that Interferon Regulatory Factor 7 (IRF7) is upregulated in adipose-derived stromal cells (MSC) of 12 months-old (middle-age) mice compared with 1 month-old mice. To go in depth into the role of IRF7 in aging of MSC we knocked-down it in 12 months MSC and assessed the transcriptional changes though whole-genome microarray analysis. We investigated the transcriptional changes induced by the Interferon Regulatory Factor 7 (IRF7) knock-down in mesenchymal stromal cells established from the inguinal fat pad of 12-months-old mice.
2021-03-10 | GSE168533 | GEO
Project description:Influenza Vaccines Differentially Regulate the Interferon Response in Human Dendritic Cell Subsets
| PRJNA322316 | ENA
Project description:Intron retention (IR) has emerged as an important mechanism of gene expression control. Despite this, the factors that control IR events remain poorly understood. We observed consistent IR in one intron of the Irf7 gene and identified Bud13 as an RNA-binding protein that acts at this intron to increase the amount of successful splicing. Deficiency in Bud13 led to increased IR, decreased mature Irf7 transcript and protein levels, and consequently to a dampened type I interferon response. This impairment of Irf7 production in Bud13 deficient cells compromised their ability to withstand VSV infection. Global analysis of Bud13 knockdown and BUD13 cross-linking to RNA revealed a subset of introns that share many characteristics with the one found in Irf7 and are spliced in a Bud13-dependent manner. Deficiency of Bud13 led to decreased mature transcript from genes containing such introns. Thus, by acting as an antagonist to IR, Bud13 facilitates the expression of genes at which IR occurs.
2018-11-15 | GSE122543 | GEO
Project description:Toll-like receptor 7 (Tlr7) deficiency-accelerated severe COVID-19 is associated with reduced production of interferons (IFNs). However, the underlying mechanisms remain elusive. Here, we demonstrate that the deficiency of Tlr7 and Irf7 globally and/or in immune cells in mice increases the severity of COVID-19 via impaired IFN activation in both immune and/or non-immune cells, leading to increased lung viral loads. These effects are associated with reduced IFN alpha and gamma production. The deficiency of Tlr7 in the infected mice tends to cause the reduced production and nuclear translocation of Interferon regulatory factor 7 (IRF7), indicative of reduced IRF7 activation. Despite higher amounts of lung viral antigen, Tlr7 or Irf7 deficiency resulted in substantially reduced production of antibodies against SARS-CoV-2, thereby delaying the viral clearance. These results highlight the importance of the activation of TLR7 and IRF7, leading to IFN production on the development of innate and adaptive immunity against COVID-19.
2024-09-05 | GSE274586 | GEO
Project description:Toll-like receptor 7 (Tlr7) deficiency-accelerated severe COVID-19 is associated with reduced production of interferons (IFNs). However, the underlying mechanisms remain elusive. Here, we demonstrate that the deficiency of Tlr7 and Irf7 globally and/or in immune cells in mice increases the severity of COVID-19 via impaired IFN activation in both immune and/or non-immune cells, leading to increased lung viral loads. These effects are associated with reduced IFN alpha and gamma production. The deficiency of Tlr7 in the infected mice tends to cause the reduced production and nuclear translocation of Interferon regulatory factor 7 (IRF7), indicative of reduced IRF7 activation. Despite higher amounts of lung viral antigen, Tlr7 or Irf7 deficiency resulted in substantially reduced production of antibodies against SARS-CoV-2, thereby delaying the viral clearance. These results highlight the importance of the activation of TLR7 and IRF7, leading to IFN production on the development of innate and adaptive immunity against COVID-19.
2024-08-20 | GSE274686 | GEO
Project description:Adenosine deaminases acting on RNA (Adar1 and Adar2) catalyze I-to-A RNA editing, a post-transcriptional mechanism involved in multiple cellular functions. The role of Adar1-dependent RNA editing in cardiomyocytes (CMs) remains unclear. Here we show that conditional deletion of Adar1 in CMs results in myocarditis progressively evolving into dilated cardiomyopathy and heart failure at only 6 months of age. Adar1 depletion drives activation of interferon signaling genes (ISGs) in the absence of apoptosis and cytokine activation, and reduces the hypertrophic response of CMs upon pressure overload. Interestingly, ablation of the cytosolic sensor MDA5 prevents cardiac ISG activation and delays disease onset, but does not rescue the long-term lethal phenotype elicited by conditional deletion of Adar1. Retention of a single catalytically inactive Adar1 allele in CMs, in combination with MDA5 depletion, however, completely restores the cardiac function and prevents heart failure. Finally, ablation of interferon regulatory factor 7 (Irf7) attenuates the phenotype of Adar1-deficient CMs to a similar extent as MDA5 depletion, highlighting Irf7 as the main regulator of the immune response triggered by lack of Adar1 in CMs.
2022-08-24 | PXD024974 | Pride
Project description:Tight regulation of macrophage immune gene expression is required to fight infection without risking harmful inflammation. The contribution of RNA binding proteins (RBPs) to shaping the macrophage response to pathogens remains poorly understood. Transcriptomic analysis revealed that a member of the serine/arginine-rich (SR) family of mRNA processing factors, SRSF7, is required for optimal expression of a cohort of interferon stimulated genes (ISGs) in macrophages. Using genetic and biochemical assays, we discovered that in addition to its canonical role in regulating alternative splicing, SRSF7 drives transcription of interferon regulatory transcription factor 7 (IRF7) to promote antiviral immunity. At the Irf7 promoter, SRSF7 maximizes STAT1 transcription factor binding and RNA polymerase II elongation via cooperation with the H4K20me1 histone methyltransferase KMT5a (SET8). These studies define an unorthodox role for an SR protein in activating transcription and reveal an unappreciated RNA binding protein-chromatin network that orchestrates macrophage antiviral gene expression.
2024-02-05 | GSE254517 | GEO
Project description:IRF7 plays a critical role in the production and amplification of the antiviral type I and III interferon response. Autosomal recessive IRF7-deficiency resulted in life-threatening influenza disease in a 3-year-old child. We studied the impact of IRF7-deficiency in non-hematopoietic tissues (fibroblasts and lung epithelial cells) as well in hematopoietic cells (peripheral blood mononuclear cells (PBMCs)). Genome-wide gene expression analysis demonstrated a profound loss of type I and III IFNs in PBMCs infected with influenza virus. PBMCs were isolated from 4 healthy donors and patients with deficiencies for IRF7 and UNC93B. The cells were infected with influenza virus A/CA/4/2009 at a multiplicity of infection (MOI) of 2 for 8 and 16 hours. Uninfected cells were cultured for 16 hours.
2015-04-07 | E-GEOD-66486 | biostudies-arrayexpress