Knock down of FTO in cervical cancer cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE133517 | GEO | 2020/02/13
REPOSITORIES: GEO
Similar Datasets
Project description:Knock down of FTO in cervical cancer cells
| PRJNA551671 | ENA
Project description:N6-methyladenosine (m6A) is the most abundant internal modification in mammalian messenger RNA (mRNA). It is installed by writer proteins and can be reversed by erasers. FTO was the first RNA demethylase shown to catalyze oxidative demethylation of m6A in RNA. Despite extensive studies, the main physiological substrates of FTO and the related functional pathways remain elusive in many systems, in particular during early mammalian development. Here, we show that FTO mediates the m6A demethylation of chromosome-associated repeat RNAs in mouse embryonic stem cells (mESCs), especially the long-interspersed element-1 family (LINE1) RNA, thereby affecting their abundances to regulate chromatin state.
2022-05-05 | GSE151704 | 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:Multifunctional N6-methyladenosine (m6A) has been revealed to be an important epigenetic component in various physiological and pathological processes, but its role in female ovarian aging remains unclear. Thus, we demonstrated m6A demethylase FTO downregulation and the ensuing increased m6A in granulosa cells (GCs) of human aged ovaries, while FTO-knockdown GCs showed faster aging-related phenotypes mediated. Using the m6A-RNA-sequence technique (m6A-seq), increased m6A was found in the FOS-mRNA-3'UTR, which is suggested to be an erasing target of FTO that slows the degradation of FOS-mRNA to upregulate FOS expression in GCs, eventually resulting in GC-mediated ovarian aging. FTO acts as a senescence-retarding protein via m6A, and FOS knockdown significantly alleviates the aging of FTO-knockdown GCs.
2021-06-15 | GSE178095 | GEO
Project description:N6-methyladenosine (m6A) modification is the major post-transcriptional modification present in mammalian mRNA. m6A controls fundamental biological processes including cell proliferation, but the molecular mechanism remains unclear. Herein, we demonstrate that the m6A demethylase fat mass and obesity-associated (FTO) controls the cell cycle by targeting cyclin D1, the key regulator required for G1 phase progression. FTO silencing suppressed cyclin D1 expression and induced G1 arrest. FTO depletion upregulated cyclin D1 m6A modification, which in turn accelerated the degradation of cyclin D1 mRNA. Importantly, m6A modification of cyclin D1 oscillates in a cell cycle-dependent manner; m6A levels were suppressed during the G1 phase and enhanced during other phases. Low m6A levels during G1 were associated with nuclear translocation of FTO from the cytosol. Furthermore, nucleocytoplasmic shuttling of FTO is regulated by Casein Kinase II-mediated phosphorylation at Thr 150 of FTO. Our results highlight the role of m6A in regulating cyclin D1 mRNA stability, and add a new layer of complexity to cell cycle regulation.
2020-03-23 | GSE133857 | GEO
Project description:N6-methyladenosine (m6A) RNA methylation is the most abundant internal chemical modifications in eukaryotic messenger RNA (mRNA) as well as long non-coding RNA (lncRNA). Recently, m6A RNA methylation research was revived by the discovery of the fat mass- and obesity-associated protein (FTO) as the first RNA demethylase, implicating that m6A RNA methylation is a reversible and dynamic modification and may have critical biological functions. Emerging evidence has shown that m6A modifications in mRNAs and lncRNAs play crucial roles in regulating RNA fate and function in biological processes in the past several years. As the first identified RNA demethylase that regulates the demethylation of target mRNAs, FTO has been reported to play an oncogenic role in leukemia and glioblastoma stem cells. To identify the target genes of FTO in melanoma cells, we used microarray analysis to determine the potential demethylation and gene targets across the whole transcriptome for FTO, and identified more than 100 genes.
2019-05-06 | GSE128961 | GEO
Project description:Fat mass and obesity-associated gene (FTO) is a member of the Fe (II) and oxoglutarate-dependent AlkB oxygenase family, and has been linked to obesity and intellectual disability. However, the role of FTO in neurodevelopment and neurogenesis remains largely unknown. Here, we show that FTO is expressed in adult neural stem cells (aNSCs) and neurons, and displays dynamic expression during postnatal neurodevelopment. The loss of FTO leads to the decreased brain size and body weight. We found that FTO deficiency could reduce the proliferation and neuronal differentiation of aNSCs in vivo, which leads to the impaired learning and memory. Given the role of FTO as a demethylase of N6-methyladenosine (m6A), we further performed the genome-wide m6A profiling and observed the dynamic m6A modification during postnatal neurodevelopment. The loss of FTO could lead to the altered m6A modifications on the mRNAs of several key components of BDNF pathway. These results together suggest that FTO play important roles in neurogenesis and learning and memory.
2017-04-20 | GSE94098 | 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: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:N6-methyladenosine (m6A) RNA methylation is the most abundant internal chemical modifications in eukaryotic messenger RNA (mRNA) as well as long non-coding RNA (lncRNA). Recently, m6A RNA methylation research was revived by the discovery of the fat mass- and obesity-associated protein (FTO) as the first RNA demethylase, implicating that m6A RNA methylation is a reversible and dynamic modification and may have critical biological functions. Emerging evidence has shown that m6A modifications in mRNAs and lncRNAs play crucial roles in regulating RNA fate and function in biological processes in the past several years. As the first identified RNA demethylase that regulates the demethylation of target mRNAs, FTO has been reported to play an oncogenic role in leukemia and glioblastoma stem cells. To identify the target genes of FTO in melanoma cells, we used m6A IP seq coupled with RNA seq to determine the potential demethylation and gene targets across the whole transcriptome for FTO, and identified more than 1,000 genes.
2019-05-06 | GSE112902 | GEO