M6A IP sequencing analysis of m6A mRNA methylation regulation by FTO in melanoma cells
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PROVIDER: PRJNA449451 | ENA |
REPOSITORIES: ENA
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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
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:Since m6A demethylases (FTO and ALKBH5) have been reported to be involved in pre-mRNA splicing regulation, we hypothesized that dynamic m6A distribution during mRNA maturation might involve removal of m6A in internal exons by FTO or ALKBH5 accompanied by splicing factors. To explore this we performed pull-down assays coupled with protein mass spectrometry.
2022-12-09 | PXD038705 | Pride
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. The goal is to determine the targets of arsenic damage including m6A RNA methylation in keratinocytes.
2021-03-01 | GSE145923 | GEO
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: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: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:The FTO gene locus has been linked to cancer and obesity through encoded N6-methyladenosine (m6A) demethylase FTO or inherited genomic variants (e.g. intronic single-nucleotide polymorphisms). Here we demonstrate that FTO-IT1, a long noncoding RNA (lncRNA) transcribed from a FTO gene intron, is upregulated during prostate cancer (PCa) progression and positively correlated with poor survival of patients with tumors only expressing wild-type p53. We show that RBM15, a mRNA/substrate binding subunit of the m6A methyltransferase complex binds and increases mRNA m6A methylation and stability of p53 transcriptional target genes; however, FTO-IT1 overexpression abolishes these effects by blocking RBM15 binding of p53 target gene mRNAs. Therapeutic targeting of FTO-IT1 restores mRNA m6A level and p53 signaling and inhibits PCa tumor growth in mice. Our study identifies FTO-IT1 lncRNA as a bono fide inhibitor of m6A methylation and p53 tumor suppression and nominates FTO-IT1 as a potential biomarker and therapeutic target of cancer.
2023-07-08 | GSE212043 | 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:Background: Despite its functional importance in various fundamental bioprocesses, the studies of N6-methyladenosine (m6A) in the heart are lacking. Methods: We performed methylated (m6A) RNA immunoprecipitation sequencing (MeRIP-seq) to map transcriptome-wide m6A in healthy and failing hearts. Results: Improving expression of FTO in failing mouse hearts attenuated the ischemia-induced increase in m6A and decrease in cardiac contractile function. This is carried out by the demethylation activity of FTO, which selectively demethylates cardiac contractile transcripts Conclusion: Collectively, our study demonstrates the functional importance of FTO-dependent cardiac m6A methylome in cardiac contraction during heart failure and provides a novel mechanistic insight into the therapeutic mechanisms of FTO.
2018-08-13 | GSE112789 | GEO