Ontology highlight
ABSTRACT:
PROVIDER: PRJNA546061 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR9211310.fastq.gz | Fastqsanger.gz | |||
| SRR9211320.fastq.gz | Fastqsanger.gz | |||
| SRR9211311.fastq.gz | Fastqsanger.gz | |||
| SRR9211312.fastq.gz | Fastqsanger.gz | |||
| SRR9211313.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:Single nucleotide polymorphisms in the FTO gene encoding a m6A demthylase are associated with obesity and cancer development. However, the functional role of FTO in the developemnt of progression of hepatocellular carcinoma (HCC) as a proteotypic obesity-associated cancer remains unclear. Here, we have generated mice with hepatic FTO deficiency (FTOL-KO) and subjected them to DEN induced HCC-development. FTOL-KO mice exhibit increased HCC burden. While control mice exhibit a dynamic regulation of FTO upon induction of liver damage, this response is abrogated in mice lacking FTO. Proteomic analyses revealed that liver damage-induced increases in FTO expression promotes m6A-demethylation of CUL4A reducing its protein expression. Functionally, knockdown of CUL4A restores the increased hepatocyte proliferation observed upon loss of FTO. Collectively, our study reveals a protective role for FTO-dependent dynamic m6A mRNA demethylation of CUL4A in the initiation of HCC development.
2020-11-03 | PXD018223 | Pride
Project description:N6-methyladenosine (m6A) is the most abundant internal modification on mammalian messenger RNA (mRNA). It is installed by a writer complex and can be reversed by erasers such as the fat mass and obesity-associated protein (FTO). Despite extensive research, the primary physiological substrates of FTO in mammalian tissues and development remain elusive. Here, we show that FTO mediates m6A demethylation of long-interspersed element-1 (LINE1) RNA in mouse embryonic stem cells (mESCs), regulating LINE1 RNA abundance and the local chromatin state, which in turn modulates transcription of LINE1-containing genes. FTO-mediated LINE1 RNA m6A demethylation also plays regulatory roles in shaping chromatin state and gene expression during mouse oocyte and embryonic development. Our results suggest broad effects of LINE1 RNA m6A demethylation by FTO in mammals.
2022-05-05 | GSE151780 | GEO
Project description:Here we use MeRIP-Seq to analyze global adenosine methylation (m6A) in mRNAs in the midbrain and striatum of Fto-deficient mice. We find that Fto deficiency leads to increased methylation within a subset of mRNAs important for neuronal signaling, including many within the dopaminergic signaling pathway. Collectively, our results show that Fto regulates demethylation of specific mRNAs in vivo, and this activity relates to control of dopaminergic transmission. Profiling of m6A in midbrain and striatum from FTO knockout mice
2013-06-15 | E-GEOD-47216 | biostudies-arrayexpress
Project description:Here we use MeRIP-Seq to analyze global adenosine methylation (m6A) in mRNAs in the midbrain and striatum of Fto-deficient mice. We find that Fto deficiency leads to increased methylation within a subset of mRNAs important for neuronal signaling, including many within the dopaminergic signaling pathway. Collectively, our results show that Fto regulates demethylation of specific mRNAs in vivo, and this activity relates to control of dopaminergic transmission. Profiling of m6A in midbrain and striatum from wild type mice
2013-06-15 | E-GEOD-47215 | biostudies-arrayexpress
Project description:The discovery of activating mutations in receptor tyrosine kinases (RTKs) leads to clinical testing of RTK inhibitors (TKIs). However, the rapid acquisition of resistance limits TKI effectiveness. Here we establish TKI-resistant cells that propagate in the absence of RTK signaling. Relative to sensitive cells, TKI-resistant cells display decreased N6-methyladenosine (m6A), a ubiquitous and reversible modification on RNA, but upregulated fat mass and obesity-associated gene (FTO), an m6A demethylase. Notably, the naïve leukemia cell populations are heterogeneous with respect to FTO levels. Cells with higher intrinsic and transient FTO expression demonstrate reduction of m6A methylation and TKI sensitivity with higher tumorigenic. Genetic or pharmacological dysfunction of FTO increases m6A abundance sensitizing resistant cells to TKIs. Mechanistically, FTO-mediated m6A demethylation promotes mRNA stability and protein translation rate, upregulating oncogenes that are indispensable for survival and proliferation. Our findings therefore establish a role of FTO-dependent m6A demethylation for TKI-resistance, offering a therapeutic window for incorporating m6A modulators in counteracting acquired TKI resistance.
2018-11-14 | GSE80481 | GEO
Project description:FTO, the first RNA demethylase discovered, mediates the demethylation of N6-methyladenosine (m6A), installed internally on messenger RNA, and N6,2′-O-dimethyladenosine (m6Am), occurring at the +1 position from the 5’ cap. Despite extensive recent research on FTO, its physiological impact on cellular processes has yet to be fully elucidated. Here, we demonstrate that the cellular distribution of FTO is distinct among different cell lines, which critically affects the access of FTO to different RNA substrates. FTO binds multiple RNA substrates, including mRNA, U6 RNA, and tRNA. It mainly targets internal m6A when located in the cell nucleus and preferentially demethylates m6Am when residing in the cytoplasm. The expression levels of transcripts containing internal m6A are associated with the alteration of the FTO more so than transcripts containing m6Am. We also discover that N1-methyladenosine (m1A) in tRNA is a main substrate of FTO, with the FTO-catalyzed demethylation of target tRNAs repressing protein synthesis. Collectively, FTO-mediated RNA demethylation affects both mRNA level and translation through distinct pathways.
2018-09-14 | GSE106395 | GEO
Project description:The fat mass and obesity-associated (FTO) protein is a well-characterized demethylase that removes N6-methyladenosine (m6A) from animal mRNAs. However, it is unclear yet how the demethylation operates in living cells. In this study, we applied genome-wide approaches to study how FTO finds its demethylation targets in human cells. We overexpressed FTO in human HeLa cells, demonstrating that FTO effectively removes m6A from the RRACH motif enriched in the 3’UTR regions and leaves m6A at other motifs unaffected. RRACH elements are clearly enriched at FTO binding sites; however, m6A has a lower tendency to be removed from the FTO-bound RRACH. Taken together with the experimental validaton results, we propose a model in which FTO effectivly recognizes m6A-containing RRACH motifs in RNAs, leading to a faster demethylation and dissociation kinetic than the association, and consequently undectable FTO-mRNA association. However, when FTO binds to the non-m6A RRACH motif, the binding has a lower dissociation kinetics, yielding the detectable FTO binding signals which would enable FTO to have roles in regulating other mRNA processing events.
2020-03-22 | GSE101953 | GEO
Project description:The fat mass and obesity-associated (FTO) protein is a well-characterized demethylase that removes N6-methyladenosine (m6A) from animal mRNAs. However, it is unclear yet how the demethylation operates in living cells. In this study, we applied genome-wide approaches to study how FTO finds its demethylation targets in human cells. We overexpressed FTO in human HeLa cells, demonstrating that FTO effectively removes m6A from the RRACH motif enriched in the 3’UTR regions and leaves m6A at other motifs unaffected. RRACH elements are clearly enriched at FTO binding sites; however, m6A has a lower tendency to be removed from the FTO-bound RRACH. Taken together with the experimental validaton results, we propose a model in which FTO effectivly recognizes m6A-containing RRACH motifs in RNAs, leading to a faster demethylation and dissociation kinetic than the association, and consequently undectable FTO-mRNA association. However, when FTO binds to the non-m6A RRACH motif, the binding has a lower dissociation kinetics, yielding the detectable FTO binding signals which would enable FTO to have roles in regulating other mRNA processing events.
2020-03-22 | GSE101954 | GEO
Project description:We performed the transcriptome-wide m6A profiling (MeRIP) with poly(A) RNA samples isolated from shoots and roots of wild type (Nipp), FTO homogeneous transgenic (FTO) and demethylation activity dead mutant variant of FTO transgenic (FTOmut) rice plants. The m6A motif and the distribution of the detected m6A sites along transcripts were consistent with reported results from previous m6A sequencing studies in plants. We then analyzed the differentially methylated m6A sites in poly(A) RNA species including those transcribed from gene loci and from repetitive elements (repeat RNAs). Compared to Nipp plants, both shoots and roots of FTO transgenic plants had showed more hypomethylated m6A peaks (hypo-m6A, 222 in shoots and 3313 in roots) than hypermethylated m6A peaks (hyper-m6A, 63 in shoots and 127 in roots) in mRNAs, while FTOmut rice had showed more hyper-m6A in shoots (349 for hyper vs 31 for hypo) but more hypo-m6A in roots (291 for hyper vs 380 for hypo) than the WT. The hypomethylated m6A peaks in FTO transgenic plants were highly enriched within 3'UTR. Gene Ontology (GO) analysis of these identified hypomethylated m6A-containing coding genes in both FTO transgenic rice shoots and roots revealed an enrichment for functional annotations related to “cellular homeostatic process”, “one-carbon and small molecule metabolic process”, and “gene expression”. We also found the extent of m6A hypomethylation was more pronounced for repeat RNAs than for mRNA species.The quantitative RNA-seq analysis that included ERCC spike-in controls confirmed that FTO plants do indeed accumulate higher overall levels of poly(A) RNA than do WT shoots and roots. Above all, FTO mediated m6A demethylation in plant mRNA and repeats RNA, leading to the activation of transcription.
2021-08-11 | GSE135549 | GEO
Project description:NAD(H) and NADP(H) are crucial coenzymes and play important and distinguishable roles in all living organisms. NAD(H) is primarily involved in catabolic reactions, whereas NADP(H) participates in anabolic reactions, such as NADP(H)-dependent reductive anabolic pathways, signal transduction, and defense against oxidative stress. Hence, regulation of the intracellular balance of NAD(H) and NADP(H) is critical. NAD(H) kinase (NADK) is the key enzyme in the de novo biosynthesis of NADP(H), catalyzing the transfer of a phosphoryl group from ATP to NAD(H), and thus plays an important role in the regulation of intracellular NAD(H)/NADP(H) balance for NADP(H)-based metabolic pathways. We used microarrays to detail the global programme of gene expression between WT and osnadk1 and identified distinct classes of up-regulated and down-regulated genes during this process.
2020-01-01 | GSE93917 | GEO