Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA397879 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5925270_1.fastq.gz | Fastqsanger.gz | |||
| SRR5925270_2.fastq.gz | Fastqsanger.gz | |||
| SRR5925280_1.fastq.gz | Fastqsanger.gz | |||
| SRR5925280_2.fastq.gz | Fastqsanger.gz | |||
| SRR5925290_1.fastq.gz | Fastqsanger.gz |
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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:Here, the m6A modification patterns in chicken liver at the acute stage of LPS-stimulated inflammation and at the normal state were explored via m6A and RNA sequencing and bioinformatics analysis. A total of 7815 m6A peaks distributed in 5066 genes were identified in the normal chicken liver, and were mostly located in the CDS, 3’UTR region and around the stop codon. At 2 h after the LPS intraperitoneal injection, the m6A modification pattern changed, and showed 1200 different m6A peaks. The hyper- and hypo-m6A peaks were differentially located, with the former mostly located in the CDS region and the later in the 3’UTR and in the region near the stop codon. The hyper- or hypo methylated genes were enriched in different GO ontrology and pathways. Co-analysis revealed a significantly positive relationship between the fold change of m6A methylation level and the relative fold change of mRNA expression. Moreover, protein and protein interaction analysis showed that genes with altered m6A methylation and mRNA expression levels were clustered in processes involved in lipid metabolism, immune response, DNA replication and protein ubiquitination. CD18 and SREBP-1 were the two hub genes clustered in the immune process and lipid metabolism, respectively. Hub gene AGPAT2 was suggested to link the immune response and lipid metabolism clusters in the PPI network. This study presented the first m6A map of broiler chicken liver at the acute stage of LPS induced inflammation. The findings may shed lights on the possible mechanisms of m6A-mediated lipid metabolism disorder in inflammation.
2022-11-24 | GSE189591 | GEO
Project description:Translation of mRNA into a polypeptide is terminated when the release factor eRF1 recognizes a UAA, UAG, or UGA stop codon in the ribosomal A site and stimulates nascent peptide release. However, stop codon readthrough can occur when a near-cognate tRNA outcompetes eRF1 in decoding the stop codon, resulting in the continuation of the elongation phase of protein synthesis. At the end of a conventional mRNA coding region readthrough allows translation into the mRNA 3’-UTR. Previous studies with reporter systems have shown that the efficiency of termination or readthrough is modulated by cis-acting elements other than stop codon identity, including two nucleotides 5’ of the stop codon, six nucleotides 3’ of the stop codon in the ribosomal mRNA channel, and stem-loop structures in the mRNA 3’-UTR. It is unknown whether these elements are important at a genome-wide level and whether other mRNA features proximal to the stop codon significantly affect termination and readthrough efficiencies in vivo. Accordingly, we carried out ribosome profiling analyses of yeast cells expressing wild-type or temperature-sensitive eRF1 and developed bioinformatics strategies to calculate readthrough efficiency, and to identify mRNA and peptide features which influence that efficiency. We found that the stop codon (nt +1 to +3), the nucleotide after it (nt +4), the codon in the P site (nt -3 to -1), and 3’-UTR length are the most influential features in the control of readthrough efficiency, while nts +5 to +9 and mRNA secondary structure in the 3’-UTR had milder effects. Additionally, we found low readthrough genes to have shorter 3’-UTRs compared to high readthrough genes in cells with thermally inactivated eRF1, while this trend was reversed in wild-type cells. Together, our results demonstrated the general roles of known regulatory elements in genome-wide regulation and identified several new mRNA or peptide features important for translation termination and readthrough.
2020-12-08 | GSE162780 | GEO
Project description:We profile transcriptome-wide m6A in female and male Anopheles sinensis and reveal that m6A is also a highly conserved modification of mRNA in mosquitoes were generated by deep sequencing, in triplicate, using illumina Novaseq™ 6000. Distinct from mammals and yeast, but similar to Arabidopsis thaliana, m6A in An. sinensis is enriched not only around the stop codon and within 3’-untranslated regions, but also around the start codon and 5’-UTR. Gene ontology analysis indicates that the unique distribution pattern of m6A in An. sinensis is associated with mosquito sex-specific pathways. In addition, the positive correlation between m6A deposition and mRNA abundance indicates that m6A can play roles in regulating gene expression in mosquitoes. Our study proposed a transcriptional regulatory network of m6A in An. sinensis, which may provide a new clue for the control of this disease-transmitting vector.
2022-05-18 | GSE193379 | GEO
Project description:Dynamic mRNA modification in the form of N6-methyladenosine (m6A) adds considerable richness and sophistication to gene regulation. The m6A mark is asymmetrically distributed along mature mRNAs, with a strong preference around the stop codon and 3’UTR. Nevertheless, approximately 35% of m6A residues are located within the coding region (CDS). It has been suggested that methylation in CDS slows down translation elongation by interfering the decoding process. However, neither the decoding feature of endogenous mRNAs nor the physiological significance of CDS m6A has been clearly defined. By integrating Ribo-seq and m6A-seq data sets, we found that CDS m6A methylation leads to ribosome pausing in a codon-specific manner. Unexpectedly, removing CDS m6A modification from these transcripts results in a further decrease of translation. A systemic analysis of RNA structural datasets revealed that CDS m6A methylation positively regulates translation by resolving mRNA secondary structures. We further demonstrate that the elongation-promoting effect of CDS methylation requires the RNA helicase-containing m6A reader YTHDC2. Our findings established the physiological significance of CDS methylation and uncovered non-overlapping function of m6A reader proteins.
2019-07-01 | GSE129194 | GEO
Project description:N6-methyladenosine (m6A) is the most abundant internal RNA modification in mRNA molecules and plays important roles in multiple important biological processes including cancer development. KIAA1429/VIRMA is an important component of m6A methyltransferase complex to facilitate depositing m6A modification in RNA molecules. Here we found that KIAA1429/VIRMA was overexpressed in breast cancer patients among other m6A related enzymes. Breast cancer patients with higher KIAA1429 expression have worse survival compared with control group. In addition, KIAA1429/VIRMA protein mislocated in cytosol in breast cancer tissues and cell lines. KIAA1429/VIRMA depletion reduced breast cancer cell proliferation and migration. Mechanism studies showed that cytosolic expressed KIAA1429/VIRMA interacted with m6A reader protein IGF2BP3 and stabilized expression of m6A-modified HAS2 expression. HAS2 is downstream of KIAA1429/VIRMA to mediate breast cancer cell proliferation and migration and has positive correlation with KIAA1429/VIRMA expression in cancer patients.
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Project description:Here, we use a novel technique for locating regions of N6-adenosine methylation (m6A) throughout the transcriptome and present a profile of m6A sites in the mouse brain. Our use of methylated RNA immunoprecipitation combined with RNA-seq (MeRIP-Seq) identifies thousands of RNAs which contain m6A sites. In addition, we find that regions of m6A formation are particularly enriched near stop codons, which might provide clues into the potential funciton of this highly prevalent RNA modificaiton. Examination of m6A sites in murine brain RNA.
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Project description:To identify m6A-regulated mRNA targets affected by VIRMA overexpression we compared m6A peak abundance measured via m6A RNA immunoprecipitation sequenc-ing in SKBR3 cells overexpressing full-length VIRMA and eGFP control
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Project description:Here, we use a novel technique for locating regions of N6-adenosine methylation (m6A) throughout the transcriptome and present a profile of m6A sites in the mouse brain. Our use of methylated RNA immunoprecipitation combined with RNA-seq (MeRIP-Seq) identifies thousands of RNAs which contain m6A sites. In addition, we find that regions of m6A formation are particularly enriched near stop codons, which might provide clues into the potential funciton of this highly prevalent RNA modificaiton. Examination of m6A sites in murine brain RNA and human embryonic kidney cells.
2012-12-31 | E-GEOD-34734 | biostudies-arrayexpress
Project description:To elucidate the molecular mechanism by which cardiac-hypertrophy-associated piRNA (CHAPIR) regulates m6A modification, we performed m6A methylated RNA immunoprecipitation sequencing (MeRIP-seq) in control or CHAPIR-overexpressing mice heart. The sequential analysis of m6A peaks showed that RGACH motif was highly enriched within m6A sites in heart and that is aligning with the classical consensus sequence of mammals ‘RGACH’, where ‘R’ indicates purine (A/G) and ‘H’ indicates non-guanine base (A/C/U). In CHAPIR treated heart, m6A mostly occurred in mRNAs (89.5%) and only about 10.5% were identified in non-coding RNAs. The majority of mRNAs contain one or two m6A peaks (89.2%) and 10.8% mRNA contain >2 m6A peaks . M6A peaks were predominantly distributed in coding sequences (CDSs), 3’ untranslated regions (3’UTRs) and near stop codon.
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