Binding protein of IGFBP2 3'UTR with or without m6A methylation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Yonghui Li
PROVIDER: PXD048441 | iProX | Thu Jan 11 00:00:00 GMT 2024
REPOSITORIES: iProX
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Project description:N6-methyladenosine (m6A) is a widespread internal RNA modification whose function is poorly understood. Here we report that m6A residues within the 5'UTR promote a novel form of cap-independent translation which is mediated through an interaction between m6A residues and the translation initiation factor, eIF3. We present eIF3a PAR-iCLIP data which demonstrate that eIF3 predominantly binds mRNAs within the 5'UTR. eIF3 binding sites are also in proximity to m6A residues within the 5'UTR of cellular mRNAs. Two replicates of eIF3a PAR-iCLIP in HEK293T cells.
2015-10-26 | E-GEOD-73405 | biostudies-arrayexpress
Project description:N6-methyadenosine (m6A) is enriched in 3`UTR (3` untranslated region) and near stop codon of mature polyadenylated mRNAs in mammalian systems and has regulatory roles in eukaryotic mRNA transcriptome switch. Significantly, the mechanism for this modification preference remains unknown, however. Herein we report a characterization of the full m6A methyltransferase complex in HeLa cells identifying METTL3/METTL14/WTAP/VIRMA/HAKAI/ZC3H13 as the key components, and we show that VIRMA mediates preferential mRNA methylation in 3`UTR and near stop codon. Biochemical studies reveal that VIRMA recruits the catalytic core components METTL3/METTL14/WTAP to guide region-selective methylations. Around 60% of VIRMA mRNA immunoprecipitation targets manifest strong m6A enrichment in 3`UTR. Depletions of VIRMA and METTL3 induce 3`UTR lengthening of several hundred mRNAs with over 50% targets in common. VIRMA associates with polyadenylation cleavage factors CPSF5 and CPSF6 in an RNA-dependent manner. Depletion of CPSF5 leads to significant shortening of 3`UTR of over 2,800 mRNAs, 84% of which are modified with m6A. Together our studies provide insights into m6A deposition specificity in 3`UTR and its correlation with alternative polyadenylation.
2018-03-07 | GSE102493 | GEO
Project description:N6-methyladenosine (m6A) is one of the most abundant modifications in eukaryotic RNA. Recent mapping of m6A methylomes in mammals, yeast, and plants as well as characterization of m6A methyltransferases, demethylases, and binding proteins have revealed regulatory functions of this dynamic RNA modification. In bacteria, although m6A is present in ribosomal RNA (rRNA), its occurrence in messenger RNA (mRNA) still remains elusive. Here, we used liquid chromatography-mass spectrometry (LC-MS) to calculate the m6A/A ratio in mRNA from a wide range of bacterial species, which demonstrates that m6A is an abundant mRNA modification in tested bacteria. Subsequent transcriptome-wide m6A profiling in Escherichia coli and Pseudomonas aeruginosa revealed a conserved distinct m6A pattern that is significantly different from that in eukaryotes. Most m6A peaks are located inside open reading frames (ORF), and carry a unique consensus motif (GCCAU). Functional enrichment analysis of bacterial m6A peaks indicates that the majority of m6A-modified transcripts are associated with respiration, amino acids metabolism, stress response, and small RNAs genes, suggesting potential regulatory roles of m6A in these pathways. m6A profiling in E.coli and P.aeruginosa mRNA
2015-07-08 | E-GEOD-65347 | biostudies-arrayexpress
Project description:XIST is a long non-coding RNA (lncRNA) that mediates transcriptional silencing of X chromosome genes. Here we show that XIST is highly methylated with at least 78 N6-methyladenosine (m6A) residues, a reversible base modification whose function in lncRNAs is unknown. We show that m6A formation in XIST, as well as cellular mRNAs, is mediated by RBM15 and its paralog RBM15B, which bind the m6A-methylation complex and recruit it to specific sites in RNA. This results in methylation of adenosines in adjacent m6A consensus motifs. Furthermore, knockdown of RBM15 and RBM15B, or knockdown of the m6A methyltransferase METTL3 impairs XIST-mediated gene silencing. A systematic comparison of m6A-binding proteins shows that YTHDC1 preferentially recognizes m6A in XIST and is required for XIST function. Additionally, artificial tethering of YTHDC1 to XIST rescues XIST-mediated silencing upon loss of m6A. These data reveal a pathway of m6A formation and recognition required for XIST-mediated transcriptional repression. Three to four biological HEK293T replicates were used to perform iCLIP of endogenous YTH proteins, RBM15, and RBM15B. Crosslinking induced truncations were identified using CIMS-CITS pipeline.
2016-09-07 | E-GEOD-78030 | biostudies-arrayexpress
Project description:The MeRIP-seq results showed that m6A was mainly detected in the 3’ untranslated regions (3’UTR) and near the exon stop codon. Meanwhile, m6A was confined to the consensus motif “RRACH” (R = G or A; H = A, C, or U). There were 3374 m6A peaks exhibit differentially changes in Alkbh5-null spermatocytes, including 1911 increased and 1463 decreased enrichments.
2026-06-19 | GSE280363 | GEO
Project description:To further understand the relationship between the level of gene expression and protein translation in human placenta, we focused on N6-methyladenosine: m6A, which is a methylation modification of mRNA acting as a post-transcriptional regulation which has drawn attention in recent years. It is said that m6A affects the fate of mRNA. In addition, it is thought that m6A affects gene expression in the placenta of preeclampsia which is a representative disease of perinatal period and fetal growth abnormality, and the placentas of children who were small for date (SFD) or heavy for date (HFD) were studied in addition to appropriate for date (AFD) preganancies. The SFD placentas contained half of the cases with PE. HEK293T cell was used to confirm the experimental system. PolyA RNA was purified from each tissue and cell, and libraries were prepared from immunoprecipitated (IP) samples using anti-m6A antibody and input samples, and sequenced with Hiseq 1500/2500 and RNAseq was carried out.
2019-10-10 | E-MTAB-6507 | biostudies-arrayexpress
Project description:N6-Methyladenosine (m6A) is the most abundant internal modification of eukaryotic mRNAs and regulates target transcripts throughout the mRNA life cycle. Although changes in m6A have been reported in human cancers, technical limitations have hindered a comprehensive understanding of the cancer-associated m6A landscape. Here, we used GLORI-sequencing to establish the first transcriptome-wide, single-nucleotide resolution maps of m6A in cancer. Differentially methylated transcripts were enriched in oncogenic pathways relevant to urothelial carcinoma of the bladder (UCB). We discovered two key m6A signatures in UCB: a global loss of methylation and a local hypermethylation at 3′-UTRs. Integration of RNA-sequencing data revealed that the global loss resulted from dilution of methylation marks due to increased expression of unmethylated transcripts and decreased expression of highly methylated transcripts. In contrast, local 3′-UTR hypermethylation was associated with the overexpression of VIRMA, a component of the m6A writer complex, which was linked to UCB progression. Our study is the first to describe the m6A epitranscriptomic landscape of cancer at single-base resolution and provides first insights into the processes that generate its characteristic signatures.
2025-07-18 | GSE281750 | GEO
Project description:N6-Methyladenosine (m6A) is the most abundant internal modification of eukaryotic mRNAs and regulates target transcripts throughout the mRNA life cycle. Although changes in m6A have been reported in human cancers, technical limitations have hindered a comprehensive understanding of the cancer-associated m6A landscape. Here, we used GLORI-sequencing to establish the first transcriptome-wide, single-nucleotide resolution maps of m6A in cancer. Differentially methylated transcripts were enriched in oncogenic pathways relevant to urothelial carcinoma of the bladder (UCB). We discovered two key m6A signatures in UCB: a global loss of methylation and a local hypermethylation at 3′-UTRs. Integration of RNA-sequencing data revealed that the global loss resulted from dilution of methylation marks due to increased expression of unmethylated transcripts and decreased expression of highly methylated transcripts. In contrast, local 3′-UTR hypermethylation was associated with the overexpression of VIRMA, a component of the m6A writer complex, which was linked to UCB progression. Our study is the first to describe the m6A epitranscriptomic landscape of cancer at single-base resolution and provides first insights into the processes that generate its characteristic signatures.
2025-07-18 | GSE281749 | GEO
Project description:The cholestasis frequently occurs in patients with inflammatory processes. However, the mechanisms of inflammation in inducing cholestasis are still unclear. Here, by using lipopolysaccharide (LPS)-induced cholestasis mouse models, we found that most genes encoding enzymes responsible for bile acid biosynthesis were downregulated in the hepatic tissues. Notably, among these genes, only Cyp7b1 was directly reduced by LPS in hepatocytes. The content of UDCA was decreased in the liver of inflammation-model mice which might be caused by the downregulation of Cyp7b1, and UDCA supplementation could alleviate the cholestasis and liver injury caused by LPS. Mechanistically, we observed that the level of m6A methylation in the 3’-UTR of Cyp7b1 mRNA was decreased, and inhibition of m6A methylation could reduce the expression of Cyp7b1 in Hep1-6 cells. Finally, a novel short variant FTO was identified to be upregulated in the liver of mice with LPS, and knockdown of the short variant FTO could rescue the expression of Cyp7b1 by improving the m6A modification in its mRNA, and then mitigate the cholestasis and liver injury in mice with LPS treatment. Collectively, our study uncovers that LPS-induced inflammation results in cholestasis by upregulating the expression of a short variant FTO, which subsequently leads to the reduction of Cyp7b1 mRNA by removing its m6A modification at the 3’-UTR region.
2025-11-07 | MTBLS10713 | MetaboLights
Project description:N6-methyladenosine (m6A) is a widespread reversible chemical modification of RNAs, implicated in many aspects of RNA metabolism. Little quantitative information exists as to either how many transcript copies of particular genes are m6A modified (âm6A levelsâ), or the relationship of m6A modification(s) to alternative RNA isoforms. To deconvolute the m6A epitranscriptome, we developed m6A level and isoform-characterization sequencing (m6A-LAIC-seq). We found that cells exhibit a broad range of non-stoichiometric m6A levels with cell type specificity. At the level of isoform characterization, we discovered widespread differences in use of tandem alternative polyadenylation (APA) sites by methylated and nonmethylated transcript isoforms of individual genes. Strikingly, there is a strong bias for methylated transcripts to be coupled with proximal APA sites, resulting in shortened 3â untranslated regions (3â-UTRs), while nonmethylated transcript isoforms tend to use distal APA sites. m6A-LAIC-seq yields a new perspective on transcriptome complexity and links APA usage to m6A modifications. m6A-LAIC-seq of H1-ESC and GM12878 cell lines, each cell line has two replicates
2016-06-24 | E-GEOD-66086 | biostudies-arrayexpress