Similar Datasets
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: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.
2012-08-31 | GSE31963 | GEO
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:Methods: Total RNA was prepared from control and RBM39 siRNAs transfected in T47D cells and subsequently used for deep sequencing, in duplicates.
2021-04-13 | GSE144376 | GEO
Project description:ADARs are the primary factors underlying A-to-I editing in metazoans. We conducted the first global study of ADAR1-RNA interaction in human cells using CLIP-Seq. In contrast to the expected predominant binding of ADAR1 to Alu repeats, thousands of CLIP sites were located in non-Alu regions. This unexpectedly frequent non-Alu binding enabled discovery of transcriptome-wide functional and biophysical targets of ADAR1 in the regulation of mRNA processing including alternative 3' UTR usage and alternative splicing. In addition, a global analysis of ADAR1 binding to non-Alu regions also revealed its primary interaction with microRNA (miRNA) transcripts in the nucleus, which subsequently affected expression levels of mature miRNAs. A complex global picture was revealed regarding the dependence of this function on the double-stranded RNA binding domains or deaminase activity. Our study unfolded a broad landscape of the diverse functional roles of ADAR1. To identify ADAR binding dependent miRNA defferential expression profiles, U87MG cells were transfected with ADAR1 overexpression vector, RNA binding mutant (EAA and E912A), siRNA of ADAR1 or controls.
2015-03-11 | E-GEOD-55362 | biostudies-arrayexpress
Project description:This study aims to delineate the role of ADAR1 in human cells beyond its canonical function as an interferon-stimulated gene (ISG). Human monocyte-derived macrophages were subjected to RNA interference targeting either pan-ADAR1 (both isoforms) or the p150 isoform specifically. Quantitative proteomic analyses were performed using state-of-the-art isobaric tandem mass tag (TMT) labeling coupled with liquid chromatography–tandem mass spectrometry (LC-MS/MS). Strikingly, silencing of ADAR1 significantly impacted prototypical macrophage functions, including endocytosis, cholesterol metabolism, and lysosomal processing, without concurrent induction of pro-inflammatory or ISG responses. Pan-ADAR1 silencing resulted in upregulation of proteins involved in lysosomal function and cholesterol processing, whereas selective depletion of ADAR1-p150 led to downregulation of pathways associated with phagocytosis and endocytosis. Moreover, loss of pan-ADAR1 caused a marked downregulation of cell-cycle and p53 signaling pathways, suggesting a potential role for the ADAR1-p110 isoform in regulating cell proliferation. Collectively, these data define previously unappreciated proteomic alterations driven by ADAR1 that influence fundamental macrophage functions beyond its established ISG role.
2026-02-13 | PXD073582 | Pride
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:In this study, we found that ADAR1 reduces the levels of double-stranded RNAs (dsRNAs) derived from both nuclear and mitochondrial transcripts. To elucidate how ADAR1 controls mitochondrial dsRNA (mt-dsRNA) accumulation, we performed quantitative mass spectrometry on mitochondrial protein fractions from wild-type and ADAR1-deficient cells, aiming to identify mitochondrial protein mediators involved in ADAR1-dependent dsRNA regulation.
2026-01-23 | PXD069896 | Pride
Project description:The purpose of this study was to examine the role of ZBP1 in the phenotype that develops when ADAR1 activity is missing, in particular when the Zα domain of ADAR1 is mutated. Mice homozygous for a Zα domain-mutant allele of Adar1 (Adar1mZα/mZα mice) were compared with control mice carrying one mZα allele and one wild type allele of Adar1 (Adar1wt/mZα mice) and with mice carrying one mZα and one null Adar1 allele (Adar1-/mZα mice). Adar1-/mZα mice were also compared with mice additionally deficient in ZBP1 (Adar1-/mZα Zbp1-/- mice). Given the early postnatal lethal phenotype that develops in Adar1-/mZα mice, comparisons were made in RNA isolated from spleen tissue from newborn mice of each genotype (5 mice per genotype).
2022-04-27 | E-MTAB-10953 | biostudies-arrayexpress
Project description:To understand how ADAR1 controls genome stability, affinity purification and mass spectrometry were employed to identify the interactomes of ADAR1 with cellular extracts from HeLa cells stably expressing FLAG-ADAR1.Mass spectrometry analysis of FLAG-ADAR1 associated proteins. The differential protein bands of the immunoprecipitates from cellular extracts of HeLa cells were retrieved from silver stained SDS-PAGE, digested with trypsin and analyzed by mass spectrometry.
2022-11-15 | PXD038167 |