FTO-Dependent m6A Regulates Cardiac Function During Remodeling and Repair
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA448982 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6952710.fastq.gz | Fastqsanger.gz | |||
| SRR6952703.fastq.gz | Fastqsanger.gz | |||
| SRR6952704.fastq.gz | Fastqsanger.gz | |||
| SRR6952705.fastq.gz | Fastqsanger.gz | |||
| SRR6952706.fastq.gz | Fastqsanger.gz |
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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
Project description:Cardiac fibrosis is common in cardiovascular diseases. N6-methyladenosine (m6A) is one of the most common modifications in eukaryotic mRNAs. Previous research has suggested that m6A modification is vital in cardiovascular diseases. The underlying targets of FTO were selected through transcriptome sequencing (RNA-seq) combined with methylated RNA immunoprecipitation sequencing (MeRIP-seq). According to MeRIP-seq and RNA-seq, FTO inhibited collagen synthesis in CFs.
2024-03-01 | GSE257546 | GEO
Project description:Cardiac fibrosis is common in cardiovascular diseases. N6-methyladenosine (m6A) is one of the most common modifications in eukaryotic mRNAs. Previous research has suggested that m6A modification is vital in cardiovascular diseases. The underlying targets of FTO were selected through transcriptome sequencing (RNA-seq) combined with methylated RNA immunoprecipitation sequencing (MeRIP-seq). According to MeRIP-seq and RNA-seq, FTO inhibited collagen synthesis in CFs.
2024-03-03 | GSE259328 | 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 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: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:FTO suppresses cardiac fibrosis after myocardial infarction via m6A-mediated epigenetic modification
| PRJNA1080202 | ENA
Project description:Our understanding of posttranscriptional modifications that decorate RNA, a regulatory layer positioned between DNA and proteins, is in its infancy. N6-methyladenosine (m6A) is the most prevalent internal modification in messenger RNAs that is installed and erased by m6A methyltransferases and demethylases. The importance of these enzymes in cancer is rapidly emerging, yet information of their specific mode of actions during disease progression remain largely unknown. In the present study, we report that the m6A RNA demethylase FTO controls EMT and invasion in cancer through regulation of the Wnt pathway. We find that loss of FTO, in contrast to acute myeloid leukemia, is frequent in many cancer types, including breast and prostate cancers. Knockdown of FTO promotes tumor progression – specifically migration and invasion – in breast and prostate cancer cells. Furthermore, implantation of these cells accelerates tumor progression in recipient mice in vivo. In these tumors, FTO depletion leads to m6A-dependent activation of Wnt signaling, which drives an enhanced EMT program and invasion, thus leading to poor clinical outcome. However, loss of FTO also sensitizes cancers cells to Wnt inhibition, offering a rationale for the therapeutic targeting of Wnt for cancer patients with low FTO levels. Together, our work reveals FTO as a novel regulator of EMT and an unexpected mechanism by which Wnt signals are dysregulated in tumors, providing a rationale to stratify cancer patients treated with Wnt inhibitor. These data uncover a previously unrecognized relationship between RNA modification and EMT in cancer.
2021-01-11 | GSE128580 | GEO
Project description:Our understanding of posttranscriptional modifications that decorate RNA, a regulatory layer positioned between DNA and proteins, is in its infancy. N6-methyladenosine (m6A) is the most prevalent internal modification in messenger RNAs that is installed and erased by m6A methyltransferases and demethylases. The importance of these enzymes in cancer is rapidly emerging, yet information of their specific mode of actions during disease progression remain largely unknown. In the present study, we report that the m6A RNA demethylase FTO controls EMT and invasion in cancer through regulation of the Wnt pathway. We find that loss of FTO, in contrast to acute myeloid leukemia, is frequent in many cancer types, including breast and prostate cancers. Knockdown of FTO promotes tumor progression – specifically migration and invasion – in breast and prostate cancer cells. Furthermore, implantation of these cells accelerates tumor progression in recipient mice in vivo. In these tumors, FTO depletion leads to m6A-dependent activation of Wnt signaling, which drives an enhanced EMT program and invasion, thus leading to poor clinical outcome. However, loss of FTO also sensitizes cancers cells to Wnt inhibition, offering a rationale for the therapeutic targeting of Wnt for cancer patients with low FTO levels. Together, our work reveals FTO as a novel regulator of EMT and an unexpected mechanism by which Wnt signals are dysregulated in tumors, providing a rationale to stratify cancer patients treated with Wnt inhibitor. These data uncover a previously unrecognized relationship between RNA modification and EMT in cancer.
2021-01-11 | GSE128581 | 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