Profiling dynamic RNA-protein interactions using small molecule-inducible RNA editing
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA853306 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19866011_1.fastq.gz | Fastqsanger.gz | |||
| SRR19866011_2.fastq.gz | Fastqsanger.gz | |||
| SRR19866012_1.fastq.gz | Fastqsanger.gz | |||
| SRR19866012_2.fastq.gz | Fastqsanger.gz | |||
| SRR19866013_1.fastq.gz | Fastqsanger.gz |
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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: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: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.
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Project description:Many previous studies, including the Next Generation Sequencing (NGS)-based ones, have shown the critical roles of RNA editing in biomedicine. Direct RNA sequencing emerges as another powerful technique to advance the understanding of RNA editing by new paradigms, especially in single-molecule and long-range characterization. The urgent gap is the accurate and robust identification of RNA editing at the single-molecule and single-nucleotide resolution from direct RNA sequencing. This is challenging due to the inherent nature of the context-dependence on the raw signals, which requires enormous training data with considerable diversity. Here we propose two coupled measures to address them: 1) an abductive deep learning strategy implemented as the software ReDD fully utilizes the widely accessible NGS-based RNA editing data as indirect labels of direct RNA sequencing to achieve the detection at the single-molecule level; 2) a cloud-based platform Argo-ReDD serves as a central database for assembling large and diverse data from the community to continuously train the abductive deep learning model, which also meets the community demand of a user-friendly way to perform RNA editing analyses, such as co-occurrence analysis, quantitative analysis and gene isoform-resolved analysis, based on the specific information from direct RNA sequencing.
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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:Nearly every step of RNA regulation is mediated by binding proteins (RBPs). The most common method to identify specific RBP target transcripts in vivo is by crosslinking (“CLIP” and its variants), which rely on protein-RNA crosslinking and specific antibodies. Another recently introduced method exploits RNA editing, with the hyperactive mutant catalytic domain of ADAR covalently attached to a specific RBP (“HyperTRIBE”). Both CLIP and TRIBE approaches suffer from difficulties in distinguishing real RNA targets from false negative and especially false positive signals. To critically evaluate this problem, we used fibroblasts from a mouse where every endogenous β-actin mRNA molecule was tagged with the bacteriophage MS2 RNA stem loops in the β-actin 3’ UTR; hence there is only a single bona fide target mRNA for the MS2 capsid protein (MCP). CLIP and HyperTRIBE (hereafter referred to as TRIBE) could both detect the single RNA target, albeit with some false positives (transcripts lacking the MS2 stem loops). Consistent false positive CLIP signals could be attributed to nonspecific antibody interactions. However, to our surprise the putative false positive TRIBE targets correlated with the location of genes spatially proximal to the β-actin gene. This result indicates that MCP-ADAR bound to β-actin mRNA contacted and edited nearby nascent transcripts, as evidenced by frequent intronic editing. Importantly, nascent transcripts on nearby chromosomes were also edited, agreeing with the interchromosomal contacts observed in chromosome paint and Hi-C. These results were repeated in human osteosarcoma cells with a randomly integrated and inducible MS2 reporter and indicated that MS2-TRIBE can be applied to a broad array of cells and transcripts. The identification of nascent RNA-RNA contacts imply that RNA-regulatory proteins such as splicing factors can associate with multiple nascent transcripts and thereby form domains of post-transcriptional activity, which increase their local concentrations. These results indicate that TRIBE combined with the MS2 system, MS2-TRIBE, is a new tool to study nuclear RNA organization and regulation.
2020-06-20 | GSE152855 | 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