Determining the methyltransferase activities of METTL3, METTL14, and METTL16
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA659033 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12510935.fastq.gz | Fastqsanger.gz | |||
| SRR12510936.fastq.gz | Fastqsanger.gz | |||
| SRR12510937.fastq.gz | Fastqsanger.gz | |||
| SRR12510938.fastq.gz | Fastqsanger.gz | |||
| SRR12510939.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 51 |
Similar Datasets
Project description:All the three enzymes, METTL3, METTL14, and METTL16, belong to methyltransferase like (METTL) family and possess the ability to deposit N6-methyladenosine (m6A) in mRNA. Via immunofluorescence staining and wertern blotting, we discovered either METTL3 or METTL14 mainly localize in nuclear, but METTL16 localizes in both cytosol and nuclei. To compare the m6A methyltransferase activities of the three m6A 'writers' and better understand their differences, MeRIP-seq (m6A-seq) was conducted with poly(A) RNAs isolaed from HEK293T cells with METTL3, 14 and 16 knockout.
2021-10-28 | GSE182607 | GEO
Project description:Determine the methyltransferase activities of METTL3, METTL14, and METTL16 via MeRIP-seq (m6A-seq)
| PRJNA757003 | ENA
Project description:METTL3 and METTL14 are considered to faithfully form the m6A writing complex in a 1:1 ratio, regulating the fate of mRNA by adding m6A modifications. However, recent studies have shown inconsistent expression and prognostic value of METTL3 and METTL14 in some tumors, suggesting that they may not be faithful in tumors. Pan-cancer analysis based on TCGA data reveals significant differences in expression, function, tumor burden correlation, and immune correlation between METTL3 and METTL14, especially in esophageal squamous cell carcinoma (ESCC). Knockdown of METTL3 significantly inhibits the cell proliferation in vitro and in vivo in ESCC EC109 cells, while the impact of METTL14 knockdown on proliferation is limited, and it cannot abolish the expression of METTL3 protein. mRNA-seq results indicate that METTL3 independently regulates the expression of 1615 genes, while only 776 genes are co-regulated by METTL3 and METTL14. Furthermore, through immunofluorescence co-localization, it is observed that METTL3 and METTL14 have certain inconsistencies in cellular localization. HPLC-MS results show that METTL3 independently binds to the Nop56p-associated pre-rRNA complex and mRNA splicing complex, separate from METTL14. Through bioinformatics and various omics studies, we have preliminarily discovered that METTL3 independently regulating tumor cell proliferation, and the participation in mRNA splicing may be a critical molecular mechanism. Our study provides an experimental basis and theoretical foundation for further understanding of the m6A writing complex and tumor therapy targeting METTL3.
2024-02-01 | PXD048886 | Pride
Project description:To identify the directly bound transcripts of METTL3, METTL14, and METTL16, RNA immunoprecipitation sequencing (RIP-seq) was conducted HEK293T stablely expressing METTL3, METTL14, and METTL16, respectively. Briefly, HEK293T cells were infected with lentivirus, pmiRNA1-3 x Flag-METTL3, pmiRNA1-3 x Flag-METTL14, and pmiRNA1-3 x Flag-METTL14, to overexpress the three METTL family members with 3 x Flag fused in the N-terminal. Only the GFP-positive cells were used for study and expanded in DMEM medium.
2021-10-28 | GSE156797 | GEO
Project description:Chemical modification of RNAs is important for post-transcriptional gene regulation. The METTL3-METTL14 complex generates most N6-methyladenosine (m6A) modifications in mRNAs, and dysregulated methyltransferase expression has been linked to numerous cancers. Here we show that m6A modification location, rather than the overall modification level, can impact oncogenesis. A gain-of-function missense mutation found in cancer patients, METTL14R298P, promotes malignant cell growth in culture and in transgenic mice. The mutant methyltransferase preferentially modifies noncanonical sites and transforms gene expression without increasing global m6A levels in mRNAs. The altered substrate specificity is intrinsic to METTL3-METTL14, helping us to propose a structural model for how the METTL3-METTL14 complex detects RNA sequences. Together, our work highlights that m6A location is important for function and that noncanonical methylation sites may impact aberrant gene expression and oncogenesis.
2024-12-21 | PXD039447 | Pride
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-10-28 | GSE156798 | GEO
Project description:Methyltransferase-like 3 (METTL3) and 14 (METTL14) are core subunits of the methyltransferase complex (MTC) that catalyzes mRNA N6-methyladenosine (m6A) modification. Despite the expanding list of m6A-dependent function of the MTC, m6A independent function of the METTL3 and METTL14 complex remains poorly understood. Here we show that genome-wide redistribution of METTL3 and METTL14 drives senescence-associated secretory phenotype (SASP) in a m6A-independent manner. METTL3 and METTL14 are necessary for SASP. However, SASP is not regulated by m6A mRNA modification. METTL14 is redistributed to the enhancers, while METTL3 is localized to the pre-existing NF-B sites within the promoters of the SASP genes during senescence. METTL3 interacts with NF-B and they are mutually dependent on their associations with the promoters of SASP genes. METTL14 but not METTL3 is necessary for function of SASP gene enhancers. METTL3 and METTL14 are required for both the tumor-promoting and immune surveillance functions of senescent cells mediated by SASP in vivo in mouse models. In summary, our results report a m6A independent function of the METTL3 and METTL14 complex in promoting SASP through regulating transcription by genome-wide redistribution of METTL14 to enhancers and METTL3 to promoters of SASP genes during senescence.
2020-12-10 | GSE159551 | GEO
Project description:Methyltransferase-like 3 (METTL3) and 14 (METTL14) are core subunits of the methyltransferase complex (MTC) that catalyzes mRNA N6-methyladenosine (m6A) modification. Despite the expanding list of m6A-dependent function of the MTC, m6A independent function of the METTL3 and METTL14 complex remains poorly understood. Here we show that genome-wide redistribution of METTL3 and METTL14 drives senescence-associated secretory phenotype (SASP) in a m6A-independent manner. METTL3 and METTL14 are necessary for SASP. However, SASP is not regulated by m6A mRNA modification. METTL14 is redistributed to the enhancers, while METTL3 is localized to the pre-existing NF-B sites within the promoters of the SASP genes during senescence. METTL3 interacts with NF-B and they are mutually dependent on their associations with the promoters of SASP genes. METTL14 but not METTL3 is necessary for function of SASP gene enhancers. METTL3 and METTL14 are required for both the tumor-promoting and immune surveillance functions of senescent cells mediated by SASP in vivo in mouse models. In summary, our results report a m6A independent function of the METTL3 and METTL14 complex in promoting SASP through regulating transcription by genome-wide redistribution of METTL14 to enhancers and METTL3 to promoters of SASP genes during senescence.
2020-12-10 | GSE141993 | GEO
Project description:Methyltransferase-like 3 (METTL3) and 14 (METTL14) are core subunits of the methyltransferase complex (MTC) that catalyzes mRNA N6-methyladenosine (m6A) modification. Despite the expanding list of m6A-dependent function of the MTC, m6A independent function of the METTL3 and METTL14 complex remains poorly understood. Here we show that genome-wide redistribution of METTL3 and METTL14 drives senescence-associated secretory phenotype (SASP) in a m6A-independent manner. METTL3 and METTL14 are necessary for SASP. However, SASP is not regulated by m6A mRNA modification. METTL14 is redistributed to the enhancers, while METTL3 is localized to the pre-existing NF-B sites within the promoters of the SASP genes during senescence. METTL3 interacts with NF-B and they are mutually dependent on their associations with the promoters of SASP genes. METTL14 but not METTL3 is necessary for function of SASP gene enhancers. METTL3 and METTL14 are required for both the tumor-promoting and immune surveillance functions of senescent cells mediated by SASP in vivo in mouse models. In summary, our results report a m6A independent function of the METTL3 and METTL14 complex in promoting SASP through regulating transcription by genome-wide redistribution of METTL14 to enhancers and METTL3 to promoters of SASP genes during senescence.
2020-12-10 | GSE141992 | GEO
Project description:Methyltransferase-like 3 (METTL3) and 14 (METTL14) are core subunits of the methyltransferase complex (MTC) that catalyzes mRNA N6-methyladenosine (m6A) modification. Despite the expanding list of m6A-dependent function of the MTC, m6A independent function of the METTL3 and METTL14 complex remains poorly understood. Here we show that genome-wide redistribution of METTL3 and METTL14 drives senescence-associated secretory phenotype (SASP) in a m6A-independent manner. METTL3 and METTL14 are necessary for SASP. However, SASP is not regulated by m6A mRNA modification. METTL14 is redistributed to the enhancers, while METTL3 is localized to the pre-existing NF-B sites within the promoters of the SASP genes during senescence. METTL3 interacts with NF-B and they are mutually dependent on their associations with the promoters of SASP genes. METTL14 but not METTL3 is necessary for function of SASP gene enhancers. METTL3 and METTL14 are required for both the tumor-promoting and immune surveillance functions of senescent cells mediated by SASP in vivo in mouse models. In summary, our results report a m6A independent function of the METTL3 and METTL14 complex in promoting SASP through regulating transcription by genome-wide redistribution of METTL14 to enhancers and METTL3 to promoters of SASP genes during senescence.
2020-12-10 | GSE141991 | GEO