RNA m1A methylation regulates glycolysis of cancer cells through modulating ATP5D
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA801615 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17804642_1.fastq.gz | Fastqsanger.gz | |||
| SRR17804642_2.fastq.gz | Fastqsanger.gz | |||
| SRR17804643_1.fastq.gz | Fastqsanger.gz | |||
| SRR17804643_2.fastq.gz | Fastqsanger.gz | |||
| SRR17804644_1.fastq.gz | Fastqsanger.gz |
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Project description:Studies on biological functions of RNA modifications such as N6-methyladenosine (m6A) in mRNA have sprung up in recent years, while the roles of N1-methyladenosine (m1A) in cancer progression remain largely unknown. We find m1A demethylase ALKBH3 can regulate the glycolysis of cancer cells via a demethylation activity dependent manner. Specifically, sequencing and functional studies confirm that ATP5D, one of the most important subunit of ATP synthase, is involved in m1A demethylase ALKBH3-regulated glycolysis of cancer cells. The m1A modified A71 at the Exon 1 of ATP5D negatively regulates its translation elongation via increasing the binding with YTHDF1/eRF1 complex, which facilitates the release of mRNA from ribosome complex. m1A also regulates mRNA stability of E2F1, which directly binds with ATP5D promoter to initiate its transcription. Targeted specific demethylation of ATP5D m1A by dm1ACRISPR system can significantly increase the expression of ATP5D and glycolysis of cancer cells. In vivo data confirm the roles of m1A/ATP5D in tumor growth and cancer progression. Our study for the first time reveals a crosstalk of mRNA m1A modification and cell metabolism, which expands the understanding of such interplays that are essential for cancer therapeutic application.
2022-02-02 | GSE195637 | GEO
Project description:Studies on biological functions of RNA modifications such as N6-methyladenosine (m6A) in mRNA have sprung up in recent years, while the roles of N1-methyladenosine (m1A) in cancer progression remain largely unknown. We find m1A demethylase ALKBH3 can regulate the glycolysis of cancer cells via a demethylation activity dependent manner. Specifically, sequencing and functional studies confirm that ATP5D, one of the most important subunit of ATP synthase, is involved in m1A demethylase ALKBH3-regulated glycolysis of cancer cells. The m1A modified A71 at the Exon 1 of ATP5D negatively regulates its translation elongation via increasing the binding with YTHDF1/eRF1 complex, which facilitates the release of mRNA from ribosome complex. m1A also regulates mRNA stability of E2F1, which directly binds with ATP5D promoter to initiate its transcription. Targeted specific demethylation of ATP5D m1A by dm1ACRISPR system can significantly increase the expression of ATP5D and glycolysis of cancer cells. In vivo data confirm the roles of m1A/ATP5D in tumor growth and cancer progression. Our study for the first time reveals a crosstalk of mRNA m1A modification and cell metabolism, which expands the understanding of such interplays that are essential for cancer therapeutic application.
2022-02-05 | GSE195703 | GEO
Project description:RNA m1A methylation regulates glycolysis of cancer cells through modulating ATP5D [Ribo and RNA-seq]
| PRJNA801861 | ENA
Project description:N1-methyladenosine (m1A) is an abundant post-transcriptional RNA modification, yet little is known about its prevalence, topology and dynamics in mRNA. Here, we show that m1A is abundant in human mRNA, with an m1A/A ratio of ~0.02%. We develop m1A-ID-Seq, based on m1A immunoprecipitation and the inherent property of m1A to stall reverse transcription, for the transcriptome-wide m1A analysis. m1A-ID-Seq identifies 901 m1A peaks (from 583 genes) in mRNA and ncRNA, and reveals a prominent feature of enrichment in the 5â-untranslated region of mRNA transcripts, distinct from that of N6-methyladenosine, the most abundant internal mammalian mRNA modification. m1A in mRNA is also reversible by ALKBH3, a known DNA/RNA demethylase. Lastly, m1A responds dynamically to stimuli and hundreds of stress-induced m1A sites are identified. Collectively, our approaches allow comprehensive analysis of m1A methylation and provide an important tool for functional studies of potential epigenetic regulation via the reversible and dynamic m1A methylation. Identification of m1A sites in human embryonic kidney cells. Comparisons of m1A profiles of wild type HEK293T with ALKBH3 knock out cell line reveals the ALKBH3 specific sites. Stress inducible m1A sites are also identified by comparing the profiles of untreated cells with stress treated cells.
2016-02-05 | E-GEOD-73941 | biostudies-arrayexpress
Project description:Activation of CD8+ T cells necessitates rapid metabolic reprogramming to fulfill the substantial biosynthetic demands of their effector functions. However, the post-transcriptional mechanisms underpinning this process remain obscure. The tRNA N1-methyladenine (m1A) modification, which plays a role in maintaining tRNA stability and modulating protein translation, has an undefined physiological function in CD8+ T cells, particularly in antitumor responses. Here, we demonstrate that the tRNA m1A 'writer' gene Trmt61a enhances the tumor-killing capacity of CD8+ T cells by regulating cholesterol biosynthesis. We find that Trmt61a expression in CD8+ T cells is upregulated upon activation and correlates positively with T cell-mediated cytotoxicity within the tumor microenvironment of colorectal cancer (CRC) patients. Deletion of Trmt61a in CD8+ T cells leads to a compromised tumor-killing function in both in vivo and in vitro assays, which is dependent on the m1A catalytic activity of TRMT61A. Mechanistically, tRNA m1A promotes antitumor immunity in CD8+ T cells by enhancing the translation of ATP citrate lyase (ACLY), a key enzyme for cholesterol biosynthesis. Supplementation with cholesterol can rescue the impaired tumor-killing function and proliferation of TRMT61A-deficient CD8+ T cells. Our findings underscore the significance of tRNA m1A modification as a regulatory checkpoint in cholesterol metabolism in CD8+ T cells, suggesting potential novel strategies for cancer immunotherapy.
2025-01-07 | GSE275602 | GEO
Project description:Studies on biological functions of RNA modifications such as N6-methyladenosine (m6A) in mRNA have sprung up in recent years, while the roles of N1-methyladenosine (m1A) in cancer progression remain largely unknown. We find m1A demethylase ALKBH3 can regulate the glycolysis of cancer cells via a demethylation activity dependent manner. Specifically, sequencing and functional studies confirm that ATP5D, one of the most important subunit of adenosine 5'-triphosphate synthase, is involved in m1A demethylase ALKBH3-regulated glycolysis of cancer cells. The m1A modified A71 at the exon 1 of ATP5D negatively regulates its translation elongation via increasing the binding with YTHDF1/eRF1 complex, which facilitates the release of message RNA (mRNA) from ribosome complex. m1A also regulates mRNA stability of E2F1, which directly binds with ATP5D promoter to initiate its transcription. Targeted specific demethylation of ATP5D m1A by dm1ACRISPR system can significantly increase the expression of ATP5D and glycolysis of cancer cells. In vivo data confirm the roles of m1A/ATP5D in tumor growth and cancer progression. Our study reveals a crosstalk of mRNA m1A modification and cell metabolism, which expands the understanding of such interplays that are essential for cancer therapeutic application.
| S-EPMC9282374 | biostudies-literature
Project description:m1A has long been known to be important in tRNA and rRNA, but we recently mapped many m1A sites in mRNA as well. m1A is found on the 5’ ends of genes, usually around the first splice site, but we have yet to understand how it effects transcript fate. Identifying the methyltransferase would be a major first step towards understanding m1A function.
2021-11-30 | PXD028832 | Pride
Project description:Dinoflagellates, a class of unicellular eukaryotic phytoplankton, exhibit minimal transcriptional regulation, representing a unique model for exploring gene expression. The biosynthesis, distribution, regulation, and function of mRNA N1-methyladenosine (m1A) remain controversial due to its limited presence in typical eukaryotic mRNA. This study found that m1A, rather than N6-methyladenosine (m6A), is the most prevalent internal mRNA modification in various dinoflagellate species, with an asymmetrically distribution along mature transcripts. In Amphidinium carterae, we identified 6549 m1A sites characterized by a non-tRNA T-loop-like sequence motif within the transcripts of 3196 genes, many involved in regulating carbon and nitrogen metabolism. With enrichment within 3'UTR, dinoflagellate mRNA m1A exhibits negative correlation with translation efficiency. Notably, nitrogen depletion led to a significant decrease in mRNA m1A. Furthermore, our analysis revealed that distinctive patterns of m1A modification influence the expression of metabolism-related genes through translation control. Thus, this study provides a comprehensive map of m1A in dinoflagellate mRNA, highlighting its crucial role as a post-transcriptional regulatory layer and enhancing the understanding of mRNA m1A modification.
2024-07-30 | GSE271240 | GEO
Project description:We developed a novel approach, m1A-seq, for high-resolution mapping of the transcriptome-wide m1A landscape, based on antibody-mediated capture followed by massively parallel sequencing Identification of m1A modified sequences in human, mouse and yeast cell lines
2016-02-10 | E-GEOD-70485 | biostudies-arrayexpress
Project description:We developed a novel approach, m1A-seq, for high-resolution mapping of the transcriptome-wide m1A landscape, based on antibody-mediated capture followed by massively parallel sequencing. Using this method we performed immunodepletion of methylated transcipts to assess the average methylation level Immunodepletion of m1A modified transcripts in human compared to the input, allows for estimation of the fraction of methylated transcripts. We compared the expression levels of sup (immunodepleted) and input methylated transcripts to deduce the fraction of m1A methylation.
2016-02-12 | E-GEOD-76057 | biostudies-arrayexpress