ADAR1 suppression in human astrocytes
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA935356 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23489142_1.fastq.gz | Fastqsanger.gz | |||
| SRR23489142_2.fastq.gz | Fastqsanger.gz | |||
| SRR23489143_1.fastq.gz | Fastqsanger.gz | |||
| SRR23489143_2.fastq.gz | Fastqsanger.gz | |||
| SRR23489144_1.fastq.gz | Fastqsanger.gz |
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Project description:ADAR1 regulates the accumulation of endeognouse double-stranded RNA (dsRNA), a pro-inflammatory/innate immune activator. The purpose of this study was to measure the effects of ADAR1 suppression in human astrocytes and determine RNAs regulated by ADAR1. Primary human astrocytes were culture and transfected with a scramble or ADAR1 siRNA. RNA was isolated from these cells for total RNA-seq to analyze changes in gene/repetitive element expression and RNA editing.
2023-09-07 | GSE225369 | GEO
Project description:Neuroinflammation is a central mechanism of brain aging and Alzheimer's disease (AD), but the exact causes of age- and AD-related neuroinflammation are incompletely understood. One potential modulator of neuroinflammation is the enzyme adenosine deaminase acting on RNA 1 (ADAR1), which regulates the accumulation of endogenous double-stranded RNA (dsRNA), a pro-inflammatory/innate immune activator. However, the role of ADAR1 and its transcriptomic targets in astrocytes, key mediators of neuroinflammation, have not been comprehensively investigated. Here, we knock down ADAR1 in primary human astrocytes via siRNA transfection and use transcriptomics (RNA-seq) to show that this results in: (1) increased expression of type I interferon and pro-inflammatory signaling pathways and (2) an accumulation of transposable element (TE) transcripts with the potential to form dsRNA. We also show that our findings may be clinically relevant, as ADAR1 gene expression declines with brain aging and AD in humans, and this is associated with a similar increase in TE transcripts. Together, our results suggest an important role for ADAR1 in preventing pro-inflammatory activation of astrocytes in response to endogenous dsRNA with aging and AD.
| S-EPMC10685929 | biostudies-literature
Project description:RNAseq analysis of cell lines with ADAR1-p150 and ADAR1-p110 knock-outs and primary human tissue samples (from GSE57353 and GSE99392 data sets) to identify sites of ADAR1 editing
2018-12-04 | GSE115127 | GEO
Project description:Aberrant RNA-editing was observed in several human tumors, but its significance is mostly unknown. Here we show that ADAR1, a ubiquitous RNA-editing enzyme, is commonly lost in metastatic melanoma cells and specimens. Experimental ADAR1 silencing significantly alters melanoma cell morphology, facilitates proliferation and cell-cycle, and increases the tumorigenicity in-vivo. A series of ADAR1 truncation mutants establishes a novel RNA-editing-independent role for ADAR1 in controlling the nuclear and cytoplasmic processing steps of miRNA biogenesis. Altered expression of ADAR1-controled miRNAs accounts for the observed phenotype. We show that the oncogenic miR-17-5p endogenously regulates ADAR1 expression and that its genomic sequence is frequently amplified in melanoma to overexpress the mature miR-17-5p form. ADAR1 and miR-17-5p are ubiquitously expressed, suggesting the generality of this mechanism. Melanoma cell line expressing low ADAR1 levels (ADAR1-Knockdown) using shRNA technique were selected for RNA extraction and hybridization on Affymetrix microarrays. We sought to examine the alterations in the genes and microRNA expression profile in the manipulated cell system, due to ADAR1 possible involvement cancer development. To that end, we selected ADAR1-knockdown (ADAR1-KD) cells that demonstrated an enhanced aggressive phenotype both in vivo and in vitro as compared to the control cells (Control).
2012-08-31 | E-GEOD-31963 | biostudies-arrayexpress
Project description:The RNA editing enzyme ADAR1 is essential for suppression of innate immune activation and pathology caused by aberrant recognition of self-RNA, a role it carries out by disrupting the duplex structure of endogenous double-stranded RNA species. A point mutation in the Z-nucleic-acid binding domain (ZBD) of ADAR1 is associated with severe autoinflammatory disease. ZBP1 is the only other ZBD-containing mammalian protein and its activation can trigger both cell death and transcriptional responses via the kinases RIPK1 and RIPK3, and the protease caspase-8. Here, we show that the pathology caused by ADAR1 ZBD mutation is driven by activation of ZBP1. We found that ablation of ZBP1 fully rescued the overt pathology caused by ADAR1 mutation, without reversing the underlying inflammatory program caused by this mutation. While loss of RIPK3 partially phenocopied the protective effects of ZBP1 ablation, combined deletion of caspase-8 and RIPK3, or of caspase-8 and MLKL, unexpectedly exacerbated the pathogenic effects of ADAR1 mutation. These findings indicate that ADAR1 is a negative regulator of sterile ZBP1 activation, and that ZBP1-dependent signaling underlies the autoinflammatory pathology caused by mutation of ADAR1.
2022-06-11 | GSE200854 | GEO
Project description:Endogenous double-stranded RNA (dsRNA) triggers pro-inflammatory signaling and has been shown to accumulate in Alzheimer’s disease (AD), but the origins of this dsRNA are incompletely understood. Transposable elements (TEs), which are non-coding DNA sequences capable of forming dsRNA, are a potential endogenous source of dsRNA in AD. We generated dsRNA immunoprecipitation (J2 dsRNA antibody) data on astrocytes treated with or without a siRNA to knock down the dsRNA editing enzyme ADAR1. We analyzed TE transcripts enriched in dsRNA pools when ADAR1 was knocked down, and we identified putative dsRNA-prone TEs, which were also present in secondary analyses of datasets profiling RNAs bound to PKR, MDA5, and the p110 isoform of ADAR1.
2025-07-25 | GSE303455 | GEO
Project description:The RNA editing enzyme ADAR1 is essential for suppression of innate immune activation and pathology caused by aberrant recognition of self-RNA, a role it carries out by disrupting the duplex structure of endogenous double-stranded RNA species. A point mutation in the Z-nucleic-acid binding domain (ZBD) of ADAR1 is associated with severe autoinflammatory disease. ZBP1 is the only other ZBD-containing mammalian protein and its activation can trigger both cell death and transcriptional responses via the kinases RIPK1 and RIPK3, and the protease caspase-8. Here, we show that the pathology caused by ADAR1 ZBD mutation is driven by activation of ZBP1. We found that ablation of ZBP1 fully rescued the overt pathology caused by ADAR1 mutation, without reversing the underlying inflammatory program caused by this mutation. While loss of RIPK3 partially phenocopied the protective effects of ZBP1 ablation, combined deletion of caspase-8 and RIPK3, or of caspase-8 and MLKL, unexpectedly exacerbated the pathogenic effects of ADAR1 mutation. These findings indicate that ADAR1 is a negative regulator of sterile ZBP1 activation, and that ZBP1-dependent signaling underlies the autoinflammatory pathology caused by mutation of ADAR1.
2022-08-10 | GSE200986 | GEO
Project description:The RNA editing enzyme ADAR1 is essential for suppression of innate immune activation and pathology caused by aberrant recognition of self-RNA, a role it carries out by disrupting the duplex structure of endogenous double-stranded RNA species. A point mutation in the Z-nucleic-acid binding domain (ZBD) of ADAR1 is associated with severe autoinflammatory disease. ZBP1 is the only other ZBD-containing mammalian protein and its activation can trigger both cell death and transcriptional responses via the kinases RIPK1 and RIPK3, and the protease caspase-8. Here, we show that the pathology caused by ADAR1 ZBD mutation is driven by activation of ZBP1. We found that ablation of ZBP1 fully rescued the overt pathology caused by ADAR1 mutation, without reversing the underlying inflammatory program caused by this mutation. While loss of RIPK3 partially phenocopied the protective effects of ZBP1 ablation, combined deletion of caspase-8 and RIPK3, or of caspase-8 and MLKL, unexpectedly exacerbated the pathogenic effects of ADAR1 mutation. These findings indicate that ADAR1 is a negative regulator of sterile ZBP1 activation, and that ZBP1-dependent signaling underlies the autoinflammatory pathology caused by mutation of ADAR1.
2022-08-10 | GSE200985 | GEO
Project description:The ADAR RNA editing enzymes deaminate adenosine bases to inosines in cellular RNAs, recoding open reading frames. Human ADAR1 mutations cause Aicardi-Goutieres Syndrome (AGS) and Adar1 mutant mice showing an aberrant interferon response and death by embryonic day E12.5 model the human disease. Searches have not identified key ADAR1 RNA editing sites recoding immune/haematopoietic proteins but editing is widespread in Alu sequences. We show that Adar1 embryonic lethality is rescued in Adar1; Mavs double mutant mice in which general antiviral responses to cytoplasmic dsRNA are prevented. We propose that inosine bases are epigenetic marks identifying cellular RNA as innate immune ÒselfÓ. Consistent with this idea we show that an editing-active cytoplasmic ADAR is required to prevent aberrant immune responses in Adar1 mutant mouse embryo fibroblasts. No dramatic increase in repetitive transcripts is observed. AGS mutations in ADAR1 affect editing by the interferon-inducible cytoplasmic ADAR1 isoform. RNA-seq expression profiling in Adar1 and Adar1/Mavs knockout mice embryos.
2014-12-19 | E-GEOD-62917 | biostudies-arrayexpress
Project description:Enterovirus infection has long been suspected as a possible trigger for type 1 diabetes. Upon infection, viral double-stranded RNA (dsRNA) is recognized by membrane and cytosolic sensors that orchestrate the type I interferon signaling and the recruitment of innate immune cells to the pancreatic islets. In this context, adenosine deaminase acting on RNA 1 (ADAR1) editing plays an important role in dampening the immune response by inducing adenosine mispairing, destabilizing the RNA duplexes and thus preventing an excessive immune activation. Here, we evaluated the role of ADAR1 in human pancreatic b cells and determined the impact of type 1 diabetes pathophysiological environment on ADAR1-dependent RNA editing. We show that both IFNα or IFNɣ/IL1β stimulation promotes ADAR1 expression and increases the A-to-I RNA editing of Alu-Containing mRNAs in EndoC-bH1 cells as well as primary human islets. We demonstrate that ADAR1 overexpression inhibits the type I interferon response signaling, while ADAR1 silencing potentiates IFNα effects. In addition, ADAR1 overexpression triggers the generation of alternative spliced RNAs, highlighting a novel role for ADAR1 as regulator of the b cell transcriptome under inflammatory conditions.
2022-11-23 | GSE214851 | GEO