6487d66b-e640-439a-b525-5746cdd12503 - samples
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PROVIDER: EGAD00001008026 | EGA |
REPOSITORIES: EGA
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Project description:N6-methyladenosine (m6A) modification plays a central role in both RNA and tumor biology. Yet comprehensive m6A epitranscriptome profiling of primary tumors remains uncharted. To fill this gap, we profiled the m6A epitranscriptome of 10 non-neoplastic lung (NL) tissues and 51 lung adenocarcinoma (LUAD) tumors, integrating them with corresponding transcriptome, proteome and extensive clinical annotation. A total of 8,030 genes are marked with m6A modification, with variable abundances across tumors. Distinct clusters and genes were found to be linked exclusively to disease progression through m6A, rather than mRNA or protein levels. In comparison with NL tissues, 430 transcripts were hypo-methylated in tumors, and 222 were hyper-methylated. Fully 69% of these had no influence on RNA abundances. Amongst these genes, EML4 emerged as a novel metastatic driver, displaying significant hyper-methylation in tumors. m6A modification promoted EML4 translation and led to widespread EML4 overexpression in primary tumors. Functionally, EML4 modulated cytoskeleton dynamics and cell morphology, triggering cellular protrusions and enhancing cellular motility, local invasion, and metastasis. Clinically, high EML4 protein abundance correlated with features of metastasis. A METTL3 small molecule inhibitor markedly diminished both EML4 m6A and protein abundance, and efficiently suppressed lung metastases in vivo. Our findings unveil a dynamic and functional epitranscriptomic landscape in lung adenocarcinoma, pinpointing the hyper-methylation of EML4 as a key driver of tumor metastasis.
2024-05-31 | GSE263726 | GEO
Project description:N6-methyladenosine (m6A) modification plays a central role in both RNA and tumor biology. Yet comprehensive m6A epitranscriptome profiling of primary tumors remains uncharted. To fill this gap, we profiled the m6A epitranscriptome of 10 non-neoplastic lung (NL) tissues and 51 lung adenocarcinoma (LUAD) tumors, integrating them with corresponding transcriptome, proteome and extensive clinical annotation. A total of 8,030 genes are marked with m6A modification, with variable abundances across tumors. Distinct clusters and genes were found to be linked exclusively to disease progression through m6A, rather than mRNA or protein levels. In comparison with NL tissues, 430 transcripts were hypo-methylated in tumors, and 222 were hyper-methylated. Fully 69% of these had no influence on RNA abundances. Amongst these genes, EML4 emerged as a novel metastatic driver, displaying significant hyper-methylation in tumors. m6A modification promoted EML4 translation and led to widespread EML4 overexpression in primary tumors. Functionally, EML4 modulated cytoskeleton dynamics and cell morphology, triggering cellular protrusions and enhancing cellular motility, local invasion, and metastasis. Clinically, high EML4 protein abundance correlated with features of metastasis. A METTL3 small molecule inhibitor markedly diminished both EML4 m6A and protein abundance, and efficiently suppressed lung metastases in vivo. Our findings unveil a dynamic and functional epitranscriptomic landscape in lung adenocarcinoma, pinpointing the hyper-methylation of EML4 as a key driver of tumor metastasis.
2024-05-31 | GSE263725 | GEO
Project description:The newly discovered dynamic N6-methyladenosine (m6A) modification plays a critical role in gene expression from a post-transcriptional level. we profiled the transcriptome-wide m6A modification in mRNAs and lncRNAs in non-targeting control A375 cells(NC) and METTL3 knockdown A375 cells(shMETTL3). Methylated RNA immunoprecipitation sequencing results revealed that the RNA m6A modification is conserved. METTL3 knockdown altered the expression of RNAs m6A modified sites in A375 cells. Finally, we show that the transcriptome-wide m6A alterations occurring in mRNAs and lncRNAs following METTL3 knockdown suggest this process plays important regulatory roles during A375 growth. This study provides a framework for applying the m6A modification regulated by METTL3 to melanoma research.
2022-01-17 | GSE183967 | GEO
Project description:N6-methyladenosine (m6A) and pseudouridine (Ψ) are the two most abundant modifications in mammalian mRNA, but the coordination of their biological functions remains poorly understood. We develop a machine learning-based nanopore direct RNA sequencing method (NanoSPA) that simultaneously analyzes m6A and Ψ in the human transcriptome. Applying NanoSPA to polysome profiling, we reveal opposing transcriptomic co-occurrence of m6A and Ψ and synergistic, hierarchical effects of m6A and Ψ on the polysome.
2024-01-06 | GSE230936 | GEO
Project description:We report the application of MeRIP-seq (m6A-specific methylated RNA immunoprecipitation) for m6A site profiling of lung tissue under Peste des petits ruminants virus (PPRV) infection.
2022-12-05 | GSE190718 | GEO
Project description:METTL16 has recently been identified as an RNA methyltransferase that installs m6A marks on a few transcripts. But its function in cytosol remains unclear. Puromycin-labelling and renilla luciferase assay revealed that METTL16 can promote translation efficiency in an m6A-independent manner. To explore the mechanism, we performed co-immunoprecipitation using METTL16 antibody and mass spectroscopy to identify its interaction proteins. Moreover, we find that METTL16 is essential for tumorigenesis of non-small cell lung cancer.
2024-08-03 | PXD032068 | Pride
Project description:As the most abundant and best-characterized internal mRNA modification, N6-methyladenosine (m6A) emerges to play a critical regulatory role in wide range of physiological and pathological processes, including gametogenesis, neuronal development, obesity and tumorigenesis. Methylated RNA immunoprecipitation coupled with next-generation sequencing (MeRIP-seq) facilitates transcriptome-wide m6A profiling, also is the most widely used technique to understand the biological significance of m6A. However, it typically requires over 100 μg of total RNA or 107 cells as input materials, hampering its application in limited samples. Here, we develop tMeRIP-seq, a transposase assisted MeRIP-seq method to achieve m6A profiling using ultra-low amount of input RNA. By marrying Tn5 tagmentation to m6A-specific immunoprecipitation, tMeRIP-seq largely improves the efficiency of library construction and reduces the input materials to as little as 60 ng total RNA or 103 cells. We apply this method on a small droplet of human blood and recapitulate the m6A profile previously reported using conventional protocol. We find tMeRIP-seq is a convenient and powerful method to examine m6A in ultra-low input material, potentially providing m6A as a new layer of bio-marker for liquid biopsy.
2021-09-07 | GSE167307 | GEO
Project description:m6A is a widespread RNA modification which plays important roles in the regulation of gene expression. Methods for the global detection of m6A rely on immunoprecipitation of methylated transcripts using m6A antibodies. However, these methods are costly and require large amounts of input RNA, making them prohibitive for many experiments. Here, we describe DART-seq, an antibody-free method for m6A detection which enables transcriptome-wide mapping of m6A residues using low amounts of input material. DART-seq can be used to obtain global m6A maps using as little as 10 nanograms of total RNA and at single-molecule resolution. This method offers several improvements over current techniques and will facilitate detection of m6A in limiting cell and tissue types.
2019-09-23 | GSE125780 | GEO
Project description:N6-methyladenosine (m6A) is the most abundant modified base in eukaryotic mRNA and has been linked to diverse effects on mRNA fate and function. Current m6A mapping approaches rely on immunoprecipitation of m6A-containing RNA fragments to identify regions of transcripts that contain m6A. This approach localizes m6A residues to 100-200 nt-long regions of transcripts. The precise position of m6A in mRNAs cannot be identified on a transcriptome-wide level because there are no chemical methods to distinguish between m6A and adenosine. Here we show that anti-m6A antibodies can induce specific mutational signatures at m6A residues after ultraviolet light-induced antibody-RNA crosslinking and reverse transcription. Similarly, we find these antibodies induce mutational signatures at N6, 2’-O-dimethyladenosine (m6Am), a nucleotide found at the first encoded position of certain mRNAs. Using these mutational signatures, we map m6A and m6Am at single-nucleotide resolution in human and mouse mRNA and identify snoRNAs as a novel class of m6A-containing ncRNAs. UV-crosslinking and immunoprecipitation with m6A-specific antibodies was used to map m6A and m6Am in cellular RNA with single nucleotide resolution.
2015-06-29 | E-GEOD-63753 | biostudies-arrayexpress
Project description:N6-methyladenosine (m6A) is a prevalent RNA modification that has key roles in distinct biological processes, including meiosis and early embryo development. Despite advances in methodology for m6A mapping, the applicability of current methods is limited by the need for large amounts of input material. We develop a sensitive picogram scale m6A RNA immunoprecipitation and sequencing (picoMeRIP-seq) method, also suitable for single-cell (scMeRIP-seq). We validate the down-scaling of the method by profiling m6A from picogram amounts of mouse liver polyA-selected RNA, mouse embryonic stem cells, and zebrafish zygotes. We provide proof-of-principle of m6A profiling in single mouse oocytes and preimplantation embryos. Our work opens a new avenue for studying m6A in single cells and scarce cell types in a transcriptome-wide manner.
2023-05-05 | GSE184893 | GEO