Identification of Mettl3-dependent m6A-modified mRNAs upon DNA-damage
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA716308 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14035760.fastq.gz | Fastqsanger.gz | |||
| SRR14035761.fastq.gz | Fastqsanger.gz | |||
| SRR14035762.fastq.gz | Fastqsanger.gz | |||
| SRR14035763.fastq.gz | Fastqsanger.gz |
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Project description:The goal of the study was to identify those mRNAs that are m6A-modified in a Mettl3-dependent manner under DNA-damage condition in oncogene-expressing mouse embryonic fibroblasts
2022-07-07 | GSE169343 | GEO
Project description:Purpose: Determine the differential m6A methylation pattern of Mettl3 between wildtype, Pkd1F/RC-KO and Pkd1F/RC-Mettl3-DKO mouse kidneys. Methods: m6A RNA IP using the Magna MeRIP™ m6A Kit (EMD Millipore, catalog #17-10499) was performed on P18 wildtype, Pkd1F/RC-KO and Pkd1F/RC-Mettl3-DKO mouse kidney samples. Two biological replicate samples from each genotype were sequenced. Each sample was a pool of 6 kidneys of the same genotype. The input samples were also sequenced to obtain mRNA profiles. Results: 133 mRNAs were found to be differentially hypermethylated in the Pkd1-KO kidneys compared to the control kidneys and differentially hypomethylated in the Pkd1-Mettl3-DKO kidneys compared to the Pkd1-KO kidneys. Two key pathogenic mRNAs namely, c-Myc and Avpr2 were identified and validated as Mettl3 targets. The mRNA transcript levels were unchanged between Pkd1-KO and Pkd1-Mettl3-DKO kidneys. Conclusion: Mettl3/m6A promotes translation of pathogenic mRNAs to mediate cystogenesis in mouse models of ADPKD.
2021-02-03 | GSE165956 | GEO
Project description:The N6-methyladenosine (m6A) mRNA modification and the mitochondrial respiratory chain (MRC) hold paramount importance in the advancement of MASLD. This study thoroughly investigates the relationship and impact of m6A mRNA modification and mitochondrial function in the progression of MASLD. Here we report that the mRNA and protein levels of mitochondrial respiratory chain (MRC) subunits showed inconsistent trends in vivo experiments. Abnormal m6A modification and mitochondrial dysfunction in MASLD were attributed to the upregulation of methyltransferase like 3 (Mettl3) and the downregulation of YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) induced by high-fat foods. Mettl3 promoted the MRC's function. However, knockout of the reader protein YTHDF1, which plays a crucial role in the m6A modification process, counteracted the effect of Mettl3 and suppressed MRC. In MASLD, damage to the MRC may be regulated by the Mettl3-m6A-YTHDF1 complex axis, especially by the role of YTHDF1. Our research has offered a novel perspective on the involvement of m6A mRNA methylation in the pathogenesis of MASLD.
2024-09-20 | PXD047819 | Pride
Project description:Methyltransferase-like 3 (METTL3) is the predominant catalytic enzyme which forms a stable complex with METTL14 and WTAP to promote m6A methylation in the nucleus. Recently, accumulating evidence has shown that METTL3 can express in the cytoplasm but the function of cytoplasmic METTL3 is not fully understood. Here, we demonstrated that METTL3 inhibition significantly delayed tumorigenesis in gastric cancer both in and ex vivo. Surprisingly, our data revealed that METTL3 could not only facilitate cancer progression via mRNA m6A modification, but also bind to numerous non-m6A-modified mRNAs, suggesting an unexpected role of METTL3 that was independent of m6A modification. Mechanistically, cytoplasm-anchored METTL3 interacted with poly(A) binding protein cytoplasmic 1 (PABPC1) to stabilize its association with cap-binding complex eIF4F, which preferentially promoted the translation of epigenetic factors without m6A modification. Clinical investigation using both xenograft models and patient samples showed that cytoplasmic distributed METTL3 was highly correlated with gastric cancer progression, and this finding could be expanded in prostate cancer patients. We therefore propose that cytoplasmic METTL3 enhances the translation of both m6A and non-m6A-modified epigenetic mRNAs thus serves as an oncogenic driver in cancer progression, and METTL3 subcellular distribution can assist diagnose and predict prognosis for cancer patients.
2022-05-16 | GSE191170 | GEO
Project description:Innate lymphoid cells (ILCs) are able to directly respond to alarmin signals and produce an array of effector molecules for immune protection and tissue homeostasis. However, how posttranscriptional machinery in ILCs execute extracellular stimuli towards robust gene expression is yet to understand. Here, we reported a cell type-specific role of N6-methyladenosine (m6A) RNA methylation in ILCs. Inducible deletion of m6A methyltransferase METTL3 had little impact on ILC maintenance in the steady state or cytokine-induced ILC1 or ILC3 activation, but dramatically diminished IL-25-triggered ILC2 response. Specific deletion of Mettl3 in ILC2 significantly attenuated cell expansion, cytokine production, inter-organ migration, and anti-helminth immunity. To investigate the molecular mechanism by which m6A modification regulates ILC2 response, we subjected ILC2 of WT and Mettl3 Klrg1Cre mice to a m6A-tagged mRNA immunoprecipitation sequencing (meRIP-seq) to identify the m6A modified mRNA.
2023-06-26 | GSE223082 | GEO
Project description:Global m6A-modified mRNAs in the uterus of wild-type mouse were analyzed by using methylated RNA immunoprecipitation sequencing (MeRIP-seq)
2022-11-18 | GSE211521 | GEO
Project description:Background: N6-methyladenosine (m6A) RNA modification plays a crucial role in various biological events and is implicated in various metabolic-related diseases. However, its role in MASLD remains unclear. This study aims to investigate the impact of Mettl3 on MASLD through multi-omics analysis, with a focus on exploring its potential mechanisms of action. Methods: MASLD mouse models were established by feeding a high-fat diet for 12 weeks, and Mettl3 stable overexpression AML12 cell models were constructed via lentiviral transfection. Subsequent transcriptomic and proteomic analyses, as well as integrated analysis between different omics datasets, were conducted. Results: Mettl3 expression significantly increased in MASLD mouse models. In the transcriptomic and proteomic analyses, we identified 848 genes with significant inconsistencies between transcriptomic and proteomic datasets. GO/KEGG enrichment terms may involve post-transcriptional modifications, particularly Mettl3-mediated m6A modification. Subsequently, through integrated proteomic analysis of Mettl3-overexpressed AML12 cell models and MASLD mouse models, we selected the top 20 co-upregulated and co-downregulated GO/KEGG terms as the main biological processes influenced by Mettl3 in MASLD. By intersecting with pathways obtained from previous integrated analyses, we identified GO/KEGG terms affected by Mettl3-induced m6A modification. Protein-protein interaction analysis of proteins involved in these pathways highlighted GAPDH, ENO1, and TPI1 as three key hub genes. Conclusion: In MASLD, Mettl3 regulates the glycolytic pathway through m6A modification, influencing the occurrence and development of the disease via the key hub genes GAPDH, ENO1, and TPI1. These findings expand our understanding of MASLD and provide strong evidence for potential therapeutic targets and drug development.
2024-09-20 | PXD050565 | Pride
Project description:We observe the increase of stress resilience in Drosophila in which the m6A methyltransferase Mettl3 is knocked down. Mettl3-dependent m6A is present in the 5' UTR of genes enriched for neurogenesis and signaling pathways, and determine that Mettl3-dependent m6A regulates the decay of heat shock chaperones. Expression levels of genes with Mettl3-dependent m6A are increased with the reduction of Mettl3 and with heat shock stress in the brain.
2022-08-26 | GSE178955 | GEO
Project description:Global m6A-modified mRNAs in wild-type mouse uterus on gestational day 4 were analyzed by using methylated RNA immunoprecipitation sequencing (MeRIP-seq)
2024-04-12 | GSE263379 | GEO
Project description:N6-methyladenosine (m6A) RNA methylation is the most abundant modification on mRNAs and plays important roles in various biological processes. The formation of m6A is catalyzed by a methyltransferase complex including methyltransferase like 3 (METTL3) as a key factor. However, the in vivo functions of METTL3 and m6A modification in mammalian development remain unclear. Here we show that specific inactivation of Mettl3 in mouse nervous system causes severe developmental defects in the brain. Mettl3 conditional knockout mice manifest cerebellar hypoplasia caused by drastically enhanced apoptosis of new born cerebellar granule cells (CGCs) in the external granular layer (EGL). METTL3 depletion induced loss of m6A modification causes extended RNA half-lives and aberrant splicing events, consequently leading to dysregulation of transcriptome-wide gene expression and premature CGC death. Our findings reveal a critical role of METTL3-mediated m6A in regulating the development of mammalian cerebellum.
2018-07-15 | GSE100528 | GEO