Dataset Information

M6A Reader: Epitranscriptome Target Prediction and Functional Characterization of N 6-Methyladenosine (m6A) Readers.

ABSTRACT: N 6-methyladenosine (m6A) is the most abundant post-transcriptional modification in mRNA, and regulates critical biological functions via m6A reader proteins that bind to m6A-containing transcripts. There exist multiple m6A reader proteins in the human genome, but their respective binding specificity and functional relevance under different biological contexts are not yet fully understood due to the limitation of experimental approaches. An in silico study was devised to unveil the target specificity and regulatory functions of different m6A readers. We established a support vector machine-based computational framework to predict the epitranscriptome-wide targets of six m6A reader proteins (YTHDF1-3, YTHDC1-2, and EIF3A) based on 58 genomic features as well as the conventional sequence-derived features. Our model achieved an average AUC of 0.981 and 0.893 under the full-transcript and mature mRNA model, respectively, marking a substantial improvement in accuracy compared to the sequence encoding schemes tested. Additionally, the distinct biological characteristics of each individual m6A reader were explored via the distribution, conservation, Gene Ontology enrichment, cellular components and molecular functions of their target m6A sites. A web server was constructed for predicting the putative binding readers of m6A sites to serve the research community, and is freely accessible at: http://m6areader.rnamd.com.

SUBMITTER: Zhen D

PROVIDER: S-EPMC7431669 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

m6A Reader: Epitranscriptome Target Prediction and Functional Characterization of N 6-Methyladenosine (m6A) Readers.

Zhen Di D Wu Yuxuan Y Zhang Yuxin Y Chen Kunqi K Song Bowen B Xu Haiqi H Tang Yujiao Y Wei Zhen Z Meng Jia J

Frontiers in cell and developmental biology 20200811

N 6-methyladenosine (m6A) is the most abundant post-transcriptional modification in mRNA, and regulates critical biological functions via m6A reader proteins that bind to m6A-containing transcripts. There exist multiple m6A reader proteins in the human genome, but their respective binding specificity and functional relevance under different biological contexts are not yet fully understood due to the limitation of experimental approach ...[more]

PMID: 32850851

Similar Datasets

Project description:Aortic dissection (AD) develops pathological changes in the separation of the true and false aortic lumen, with high lethality. m6A methylation and oxidative stress have also been shown to be involved in the onset of AD. Through bioinformatics methods, three differentially expressed m6A regulators (YTHDC1, YTHDC2, and RBM15) were excavated from the GSE52093 dataset in the Gene Expression Omnibus (GEO) database, and functional enrichment analysis of the differentially expressed genes (DEGs) regulated by m6A regulators was performed. Then, the genes with oxidative stress-related functions among these genes were found. The protein interaction network of the oxidative stress-related genes and the competing endogenous RNA- (ceRNA-) miRNA-mRNA network were constructed. Among them, DHCR24, P4HB, and PDGFRA, which have m6A differences in AD samples, were selected as key genes. We also performed immune infiltration analysis, as well as cell-gene correlation analysis, on samples from the dataset. The results showed that YTHDC1 was positively correlated with macrophage M1 and negatively correlated with macrophage M2. Finally, we extracted AD and healthy aorta RNA and protein from human tissues that were taken from AD patients and patients who received heart transplants, performed quantitative real-time PCR (qRT-PCR) on YTHDC2 and RBM15, and performed qRT-PCR and western blot (WB) detection on YTHDC1 to verify their differences in AD. The mRNA and protein levels of YTHDC1 were consistent with the results of bioinformatics analysis and were downregulated in AD. Immunofluorescence (IF) was used to colocalize YTHDC1 and endothelial cell marker CD31. After knocking down YTHDC1 in human umbilical vein endothelial cells (HUVECs), reactive oxygen species (ROS) levels had a tendency to increase and the expression of peroxide dismutase SOD2 was decreased. This study provides assistance in discovering the role of m6A regulator YTHDC1 in AD. In particular, m6A modification participates in oxidative stress and jointly affects AD.

Dataset Information

M6A Reader: Epitranscriptome Target Prediction and Functional Characterization of N 6-Methyladenosine (m6A) Readers.

Publications

m<sup>6</sup>A Reader: Epitranscriptome Target Prediction and Functional Characterization of <i>N</i> <sup>6</sup>-Methyladenosine (m<sup>6</sup>A) Readers.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets