Global landscape of RNA editing in hematopoiesis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA596237 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10721352_1.fastq.gz | Fastqsanger.gz | |||
| SRR10721352_2.fastq.gz | Fastqsanger.gz | |||
| SRR10721353_1.fastq.gz | Fastqsanger.gz | |||
| SRR10721353_2.fastq.gz | Fastqsanger.gz | |||
| SRR10721354_1.fastq.gz | Fastqsanger.gz |
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Project description:Adenosine-to-inosine (A-to-I) RNA editing plays a vital role in many biological processes. Our previous study has demonstrated that the hematopoietic stem and progenitor cells (HSPCs) deficient in RNA editing cannot reconstitute the irradiated recipients in vivo. However, the overall profile of RNA editome in hematopoiesis has not been established and the underlying mechanism is poorly understood. Here, we sorted 12 murine adult hematopoietic cell populations, and performed deep RNA and DNA sequencing. We depicted the first landscape of RNA editing in hematopoietic cells and identified 30,796 editing sites in total. Although total editing frequency was stable across the 12 hematopoietic populations, we identified stage-specific and group-specific editing genes, and uncovered multiple famous hematopoietic regulators were dynamically edited. By charactering group specific editing genes, we found that the Azin1 (antizyme inhibitor 1) was highly edited in HSPCs, which was required for HSPCs differentiation. A-to-I editing of Azin1 transcript resulted in serine-to-glycine substitution at residue 367 of AZIN1, induced its translocation from cytoplasm to nucleus, enabled its higher binding affinity with DDX1 (DEAD box polypeptide 1) in nucleus further to alter the chromatin distribution of DDX1, resulting in multiple hematopoietic regulators expression change. Collectively, this study provided the first landscape of RNA editing in hematopoietic cascade and uncovered the mechanism of A-to-I editing of Azin1 in regulating HSPCs function.
2020-09-29 | GSE142216 | GEO
Project description:High-throughput sequencing screens suggest that RNA editing, which consists in the substitution of adenosine with inosine by the RNA-specific adenosine deaminase (ADAR) enzyme, occurs at several thousand positions across the human genome. Recent evidences have shown that RNA-editing could promote proliferation and carcinogenesis; however, the general principles of ADAR activity on the transcriptome and how ADAR is controlled in cancers remain to be established. The main aim of this project was to investigate the phenomenon of RNA editing in breast and other cancers. The frequency of A-to-I editing was evaluated in 58 breast cancers equally distributed among the different molecular subtypes and 10 normal breast tissues. The analysis was focused on defining: the relationship between the global amount of editing and ADAR expression; the ability to predict the level of editability of specific sites; the distribution of editing in normal and tumour samples and among different breast cancer subtypes; and the clinical, pathological and genomic factors affecting editing.
| EGAS00001000495 | EGA
Project description:We report the development of an ELISA-based chemiluminescent assay to measure global levels in A-to-I editing. We directly compare this performance to RNA-seq analysis using the Alu Editing Index. These attached datasets represent sequenced mRNA isolated from HEK293T cells transfected with increasing amounts of ADAR1 to induce a global increase in A-to-I RNA editing activity.
2021-04-07 | GSE171545 | GEO
Project description:The project aims to evaluate the contribution of ADAR1 RNA editing to B cell lymphomagenesis, specifically in diffuse large B cell lymphoma (DLBCL). Within our DLBCL cohort, RNA editing targets transcripts within known lymphoma-driving pathways such as apoptosis, p53 and NF-kB signaling, as well as the previously unrecognized RIG-I-like pathway. In the latter context, we show that ADAR1-mediated editing in the MAVS transcript correlates with increased MAVS protein expression levels, associating with increased interferon/NF-kB signaling and increased T cell exhaustion. To confirm this mechanism, we have performed LC-MSMS analysis on a DLBCL cell line (RCK8) in the presence or absence of ADAR1 (Figure S11D ). Additionally, using targeted RNA base editing tools to restore editing within MAVS 3'UTR in ADAR1-deficient cells, we demonstrate that editing is likely to be causal to an increase in downstream signaling in the absence of activation by canonical nucleic acid receptor sensing. To confirm that this signaling increase depends on an increase of MAVS protein upon specific editing, we have performed LC-MSMS analysis on the same samples (Figure 4G).
2023-07-20 | PXD041549 | Pride
Project description:This dataset is a part of a bigger work on RNA editing in D. melanogaster brain. We present Orbitrap spectra searched against a customized database of Drosophila proteome with introduction of variants provided by RNA editing. Tree files reflect 3 technical replicates.
2019-03-13 | PXD004949 | Pride
Project description:This dataset is a part of a bigger work on RNA editing in D. melanogaster brain. We present Orbitrap spectra searched against a customized database of Drosophila proteome with introduction of variants provided by RNA editing. Three files reflect 3 technical replicates.
2018-10-25 | PXD009590 | Pride
Project description:Systematic evaluation of the impact of genetic variants is critical for the study and treatment of human physiology and disease. While specific mutations can be introduced by genome engineering, we still lack scalable approaches that are applicable to the important setting of primary cells, such as blood and immune cells. Here, we describe the development of massively parallel base-editing screens in human hematopoietic stem and progenitor cells. Such approaches enable functional screens for variant effects across any hematopoietic differentiation state. Moreover, they allow rich phenotyping through single-cell RNA sequencing readouts, and separately, characterization of editing outcomes through pooled single-cell genotyping. We efficiently design improved leukemia immunotherapy approaches, comprehensively identify non-coding variants modulating fetal hemoglobin expression, define mechanisms regulating hematopoietic differentiation, and probe the pathogenicity of uncharacterized disease-associated variants. These strategies will advance effective and high-throughput variant-to-function mapping in human hematopoiesis to identify the causes of diverse diseases.
2023-05-02 | GSE215253 | GEO
Project description:Purpose: RNA editing by ADAR1 is essential for hematopoietic development. The goals of this study were firstly, to identify ADAR1-specific RNA-editing sites by indentifying A-to-I (G) mismatches in RNA-seq data compared to mm9 reference genome in wild type mice that were not edited or reduced in editing frequency in ADAR1E861A editing deficient mice. Secondly, to determine the transcriptional consequence of an absence of ADAR1-mediated A-to-I editing. Methods: Fetal liver mRNA profiles of embryonic day 12.5 wild-type (WT) and ADAR1 editing-deficient (ADAR1E861A) mice were generated by RNA sequencing, in triplicate (biological replicates), using Illumina HiSeq2000. The sequence reads that passed quality filters were analyzed at the transcript level with TopHat followed by Cufflinks. qRT–PCR validation was performed using SYBR Green assays. A-to-I (G) RNA editing sites were identified as previously described by Ramaswami G. et al., Nature Methods, 2012 using Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA). RNA editing sites were confirmed by Sanger sequencing. Results: Using an optimized data analysis workflow, we mapped about 30 million sequence reads per sample to the mouse genome (build mm9) and identified 14,484 transcripts in the fetal livers of WT and ADAR1E861A mice with BWA. RNA-seq data had a goodness of fit (R2) of >0.94 between biological triplicates per genotype. Approximately 4.4% of the transcripts showed differential expression between the WT and ADAR1E861A fetal liver, with a LogFC≥1.5 and p value <0.05. A profound upregulation of interferon stimulated genes were found to be massively upregulated (up to 11 logFC) in ADAR1E861A fetal liver compared to WT. 6,012 A-to-I RNA editing sites were identified when assessing mismatches in RNA-seq data of WT and ADAR1E861A fetal liver. Conclusions: Our study represents the first detailed analysis of fetal liver transcriptomes and A-to-I RNA editing sites, with biologic replicates, generated by RNA-seq technology. A-to-I RNA editing is the essential function of ADAR1 and is required to suppress interferon signaling to endogenous RNA. Fetal liver mRNA profiles of E12.5 wild type (WT) and ADAR E861A mutant mice were generated by deep sequencing, in triplicate, using Illumina HiSeq 200.
2015-07-23 | E-GEOD-58917 | biostudies-arrayexpress
Project description:Adenosine to Inosine (A-to-I) RNA editing is a site-specific modification of RNA transcripts, catalyzed by members of the ADAR (Adenosine Deaminase Acting on RNA) protein family. RNA editing occurs in human RNA in thousands of different sites. Some of the sites are located in protein-coding regions but the majority is found in non-coding regions, such as 3âUTRs, 5âUTRs and introns - mainly in Alu elements. While editing is found in all tissues, the highest levels of editing are found in the brain. It was shown that editing levels within protein-coding regions are increased during embryogenesis and after birth and that RNA editing is crucial for organism viability as well as for normal development. In this study we characterized the A-to-I RNA editing phenomenon during neuronal and spontaneous differentiation of human embryonic stem cells (hESCs). We identified high editing levels of Alu repetitive elements in hESCs and demonstrated a global decrease in editing levels of non-coding Alu sites when hESCs are differentiating, particularly into the neural lineage. Using RNA interference, we showed that the elevated editing levels of Alu elements in undifferentiated hESCs are highly dependent on ADAR1. DNA microarray analysis showed that ADAR1 knockdown has a global effect on gene expression in hESCs and leads to a significant increase in RNA expression levels of genes involved in differentiation and development processes, including neurogenesis. Taken together, our data suggest that A-to-I editing of Alu sequences plays a role in the regulation of hESC early differentiation decisions. Two samples, One control and the second treated
2010-07-29 | E-GEOD-19719 | biostudies-arrayexpress
Project description:Adenosine-to-inosine (A-to-I) RNA editing is an epigenetic modification catalyzed by adenosine deaminases acting on RNA (ADARs), and is especially prevalent in the brain. Using microfluidics-based multiplex PCR sequencing (mmPCR-seq) to assess A-to-I editing at 146 pre-selected, conserved sites, we found that editing was generally higher in adult compared to neonatal rat brain, and that at birth, global editing was lower in prefrontal cortex than in amygdala. Prereproductive stress (PRS) affected editing at the serotonin receptor 2c, and editing at this site was significantly altered in offspring of PRS rats across two generations. Changes in ADAR expression did not correlate with editing changes induced by development or stress. Our findings indicate that mmPCR-seq can accurately detect RNA editing in rat brain samples, and confirm previous accounts of a developmental increase in RNA editing rates. Altered RNA editing rates in offspring of stress-exposed rats complements growing literature on the transgenerational effects of stress.
2017-05-24 | GSE99214 | GEO