Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PXD001007
PROVIDER: PRJNA248400 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The genome-wide identification, tissue-specificity and functional implications of Apobec-1 mediated C-to-U RNA editing remains incomplete. Deep sequencing, data filtering and validation from wild-type and Apobec-1 deficient mice revealed 56 novel editing sites in 54 intestinal mRNAs and 22 novel sites in 17 liver mRNAs (74-81% true-positive), all within 3' untranslated regions. Eleven of 17 liver RNAs shared editing sites with intestinal RNAs, while 6 sites were unique to liver. Changes in RNA editing led to corresponding changes in intestinal mRNA and protein levels in 11 genes. We found distinctive polysome profiles for several editing targets and demonstrated nuclear but not cytoplasmic editing of novel exonic sites in intestinal (but not hepatic) apoB RNA. RNA editing was validated using cell-free extracts from wild-type but not Apobec-1 deficient mice. These studies define selective, tissue-specific targets of Apobec-1 dependent RNA editing and show the functional consequences of editing are both transcript- and tissue-specific. Examination of C-to-U RNA editing in mouse liver and intestine
2014-05-23 | E-GEOD-57910 | biostudies-arrayexpress
Project description:Background: RNA editing encompasses a post-transcriptional process in which the genomically templated sequence is enzymatically altered and introduces a modified base into the edited transcript. Mammalian C-to-U RNA editing represents a distinct subtype of base modification, whose prototype is intestinal apolipoproteinB (apoB) mRNA, mediated by the catalytic deaminase Apobec-1. However, the genome-wide identification, tissue-specificity and functional implications of Apobec-1 mediated C-to-U RNA editing remains incomplete. Results: Deep sequencing, data filtering and Sanger-sequence validation of intestinal and hepatic RNA from wild-type and Apobec-1 deficient mice revealed 56 novel editing sites in 54 intestinal mRNAs and 22 novel sites in 17 liver mRNAs (74-81% Sanger sequenced validated), all within 3’ untranslated regions. Eleven of 17 liver RNAs shared editing sites with intestinal RNAs, while 6 sites were unique to liver. Changes in RNA editing led to corresponding changes in intestinal mRNA and protein levels in 11 genes. RNA editing in vivo following tissue-specific Apobec-1 adenoviral or transgenic Apobec-1 overexpression revealed that a subset of targets identified in wild-type mice were restored in Apobec-1 deficient mouse intestine and liver following Apobec-1 rescue. We found distinctive polysome profiles for several RNA editing targets and demonstrated novel exonic editing sites in nuclear preparations from intestine (but not hepatic) apoB RNA. RNA editing was validated using cell-free extracts from wild-type but not Apobec-1 deficient mice, demonstrating that Apobec-1 is required. Conclusions: These studies define selective, tissue-specific targets of Apobec-1 dependent RNA editing and show the functional consequences of editing are both transcript- and tissue-specific.
2014-06-02 | PXD001007 | Pride
Project description:The genome-wide identification, tissue-specificity and functional implications of Apobec-1 mediated C-to-U RNA editing remains incomplete. Deep sequencing, data filtering and validation from wild-type and Apobec-1 deficient mice revealed 56 novel editing sites in 54 intestinal mRNAs and 22 novel sites in 17 liver mRNAs (74-81% true-positive), all within 3' untranslated regions. Eleven of 17 liver RNAs shared editing sites with intestinal RNAs, while 6 sites were unique to liver. Changes in RNA editing led to corresponding changes in intestinal mRNA and protein levels in 11 genes. We found distinctive polysome profiles for several editing targets and demonstrated nuclear but not cytoplasmic editing of novel exonic sites in intestinal (but not hepatic) apoB RNA. RNA editing was validated using cell-free extracts from wild-type but not Apobec-1 deficient mice. These studies define selective, tissue-specific targets of Apobec-1 dependent RNA editing and show the functional consequences of editing are both transcript- and tissue-specific.
2014-05-23 | GSE57910 | GEO
Project description:<p><b>Reprinted from Roberts et al. "An APOBEC cytidine deaminase mutagenesis pattern is widespread in human cancers", Nature Genetics, 45:970-976, 2013, with permission of Nature Publishing Group:</b></p> <p>Recent studies indicate that a subclass of APOBEC cytidine deaminases, which convert cytosine to uracil during RNA editing and retrovirus or retrotransposon restriction, may induce mutation clusters in human tumors. We show here that throughout cancer genomes APOBEC-mediated mutagenesis is pervasive and correlates with APOBEC mRNA levels. Mutation clusters in whole-genome and exome data sets conformed to the stringent criteria indicative of an APOBEC mutation pattern. Applying these criteria to 954,247 mutations in 2,680 exomes from 14 cancer types, mostly from The Cancer Genome Atlas (TCGA), showed a significant presence of the APOBEC mutation pattern in bladder, cervical, breast, head and neck, and lung cancers, reaching 68% of all mutations in some samples. Within breast cancer, the HER2-enriched subtype was clearly enriched for tumors with the APOBEC mutation pattern, suggesting that this type of mutagenesis is functionally linked with cancer development. The APOBEC mutation pattern also extended to cancer-associated genes, implying that ubiquitous APOBEC-mediated mutagenesis is carcinogenic.</p>
| phs000677 | dbGaP
Project description:Recently, several studies revealed that pseudourine exists on mRNA. However, identification of ψ sites for specific PUS remains a certain ambiguity. PUS1, an important pseudouridine synthase, plays a critical role in cell growth and tumorigenesis of HCC. Here, we utilized an IP-free approach, Surveying Targets by APOBEC-Mediated Profiling (STAMP) and analyzed C-to-U editing sites to realize PUS1-bound mRNAs. And then, we identified the potential mRNA pseudouridylation targets of PUS1 by intersecting editing sites’ host genes with these that known to pseudouridylated.
2024-02-26 | GSE229980 | GEO
Project description:Apolipoprotein B-editing enzyme, catalytic polypeptide-1 (APOBEC1) is a cytidine deaminase, initially identified by its activity in converting a specific cytidine (C) to uridine (U) in apolipoprotein B (apoB) mRNA transcripts in the small intestine. Editing results in translation of a truncated apoB isoform with distinct functions in lipid transport. To address the possibility that APOBEC1 edits additional mRNAs, we developed a transcriptome-wide comparative RNA-Seq screen. We identified and validated 32 previously undescribed mRNA targets of APOBEC1 editing, all of which are located in AU-rich segments of transcript 3′ untranslated regions (3′ UTRs). Further analysis revealed several characteristic sequence features of editing targets, which were predictive for the identification of additional APOBEC1 substrates. The identification of multiple mRNA editing substrates for APOBEC1 suggests additional functions for this cytidine deaminase beyond its characterized role in lipid absorption.
2011-01-23 | GSE24958 | GEO
Project description:Human intestinal organoids (hIOs) resemble the human intestine physiologically and structurally. We recently present an in vitro maturation technique for generating mature and functional hIOs from human pluripotent stem cells (hPSCs). Here, we investigated the mechanisms of STAT3 for inducing in vitro maturation of hIOs. Using CRISPR/Cas9-mediated gene editing, STAT3 knockout (KO) human embryonic stem cell (hESC) lines were generated and characterized. By genome-wide microarray analyses, STAT3 KO hIOs showed markedly different profiles from the in vitro matured hIOs and human small intestine and the majority of genes, which are associated with intestinal development and functions, were downregulated by STAT3 KO. This study reveals important signaling pathways for the maturation of hIOs derived from hPSCs.
2019-09-30 | GSE132561 | GEO
Project description:Pioneering studies within the last few years have allowed the in vitro expansion of tissue-specific adult stem cells from a variety of endoderm-derived organs, including the stomach, small intestine and colon. Here we derived organoids from mouse gallbladder tissue (gallbladder organoids), from mouse liver (including the extrahepatic biliary ducts and gallbladder; liver organoids) and from mouse small intestine tissue (intestinal organoids). RNA was prepared from these organoids and used to assay expression of 21,258 genes using Affymetrix gene expression arrays. RNA was also prepared from mouse gallbladder, liver and small intestine tissues and used to assay gene expression in these tissues. Finally, gallbladder organoids were induced to differentiate by removing R-spondin 1 and noggin from the culture media and subjected to gene expression array analysis. RNA was extracted from mouse gallbladder organoids, differentiated gallbladder organoids, liver organoids, small intestine organoids, gallbladder tissue, liver tissue and small intestine tissue and then used for hybridization of Affymetrix gene expression microarrays.
2016-04-06 | E-GEOD-77461 | biostudies-arrayexpress
Project description:RNA binding proteins (RBPs) perform a myriad of functions and are implicated in numerous neurological diseases. To identify the targets of RBPs in small numbers of cells, we developed TRIBE, in which the catalytic domain of the RNA editing enzyme ADAR (ADARcd) is fused to a RBP. In STAMP, the ADARcd is replaced by the RNA editing enzyme Apobec (REF). Here we compared the two enzymes fused to the RBP TDP43 in human cells. Although they both identified TDP43 target mRNAs, combining the two methods more successfully identified high confidence targets. We also assayed the two enzymes in Drosophila cells in which RBP-Apobec fusions generated only low numbers of editing sites comparable to the level of control editing. This was true for two different RBPs, Hrp48 and Thor (Drosophila EIF4E-BP), and contrasted with successful RBP-ADARcd fusions. The results indicate that TRIBE is the method of choice in Drosophila.
2023-02-05 | GSE223556 | GEO
Project description:RNA binding proteins (RBPs) perform a myriad of functions and are implicated in numerous neurological diseases. To identify the targets of RBPs in small numbers of cells, we developed TRIBE, in which the catalytic domain of the RNA editing enzyme ADAR (ADARcd) is fused to a RBP. In STAMP, the ADARcd is replaced by the RNA editing enzyme Apobec (REF). Here we compared the two enzymes fused to the RBP TDP43 in human cells. Although they both identified TDP43 target mRNAs, combining the two methods more successfully identified high confidence targets. We also assayed the two enzymes in Drosophila cells in which RBP-Apobec fusions generated only low numbers of editing sites comparable to the level of control editing. This was true for two different RBPs, Hrp48 and Thor (Drosophila EIF4E-BP), and contrasted with successful RBP-ADARcd fusions. The results indicate that TRIBE is the method of choice in Drosophila.
2023-02-05 | GSE223555 | GEO