Principles of RNA methylation and their implications for biology and medicine

Zhou, Yujia; Kong, Ying; Fan, Wenguo; Tao, Tao; Xiao, Qin; Li, Na; Zhu, Xiao

doi:10.1016/j.biopha.2020.110731

Cited by 89 publications

(52 citation statements)

References 202 publications

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“…We collected 23 widely reported m6A RNA methylation regulators (2,(25)(26)(27)(28)(29), studied their expression differences in normal and cancerous tissues, and evaluated the relationship between m6A regulation of tumor-related genes and clinically relevant factors in the hematological malignancies.…”

Section: Selection Of M6a Rna Methylation Regulatorsmentioning

confidence: 99%

“…Therefore, the introduction of m6A methylation regulator into hematological malignancies is a worthy direction to be explored. N6-methyladenosine (m6A) is the most abundant form of eukaryotic mRNA modification (1,2), which occurs in the sixth nitrogen atom (N) of adenine (A). As is known to all, it plays a crucial role in the regulation of gene expression, protein transformation, and other biological activities by affecting the stability, translation efficiency, variable splicing, and localization of mRNA (2,3).…”

Section: Introductionmentioning

confidence: 99%

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Clinical and Prognostic Pan-Cancer Analysis of N6-Methyladenosine Regulators in Two Types of Hematological Malignancies: A Retrospective Study Based on TCGA and GTEx Databases

et al. 2021

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N6-methyladenosine (m6A) is one of the most active modification factors of mRNA, which is closely related to cell proliferation, differentiation, and tumor development. Here, we explored the relationship between the pathogenesis of hematological malignancies and the clinicopathologic parameters. The datasets of hematological malignancies and controls were obtained from the TCGA [AML (n = 200), DLBCL (n = 48)] and GTEx [whole blood (n = 337), blood vascular artery (n = 606)]. We analyzed the m6A factor expression differences in normal tissue and tumor tissue and their correlations, clustered the express obvious clinical tumor subtypes, determined the tumor risk score, established Cox regression model, performed univariate and multivariate analysis on all datasets. We found that the AML patients with high expression of IGF2BP3, ALKBH5, and IGF2BP2 had poor survival, while the DLBCL patients with high expression of METTL14 had poor survival. In addition, “Total” datasets analysis revealed that IGF2BP1, ALKBH5, IGF2BP2, RBM15, METTL3, and ZNF217 were potential oncogenes for hematologic system tumors. Collectively, the expressions of some m6A regulators are closely related to the occurrence and development of hematologic system tumors, and the intervention of specific regulatory factors may lead to a breakthrough in the treatment in the future.

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Section: Selection Of M6a Rna Methylation Regulatorsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical and Prognostic Pan-Cancer Analysis of N6-Methyladenosine Regulators in Two Types of Hematological Malignancies: A Retrospective Study Based on TCGA and GTEx Databases

et al. 2021

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“…In addition, bases that have undergone m6A modification are de-methylated in the presence of two enzymes, FTO and ALKBH5, making the m6A reaction reversible (Chen et al, 2019). Recent studies have shown that m6A is closely involved in many biological functions, such as the regulation of the Epithelial-to-mesenchymal transition (EMT) process, the DNA damage response, gene translation, autophagy, adipogenesis, and the determination of stem cell fate (Zhou et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Analysis of the Transcriptome-Wide m6A Methylome in Pterygium by MeRIP Sequencing

Jiang

Zhang

et al. 2021

Front. Cell Dev. Biol.

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AimPterygium is a common ocular surface disease, which is affected by a variety of factors. Invasion of the cornea can cause severe vision loss. N6-methyladenosine (m6A) is a common post-transcriptional modification of eukaryotic mRNA, which can regulate mRNA splicing, stability, nuclear transport, and translation. To our best knowledge, there is no current research on the mechanism of m6A in pterygium.MethodsWe obtained 24 pterygium tissues and 24 conjunctival tissues from each of 24 pterygium patients recruited from Shanghai Yangpu Hospital, and the level of m6A modification was detected using an m6A RNA Methylation Quantification Kit. Expression and location of METTL3, a key m6A methyltransferase, were identified by immunostaining. Then we used m6A-modified RNA immunoprecipitation sequencing (MeRIP-seq), RNA sequencing (RNA-seq), and bioinformatics analyses to compare the differential expression of m6A methylation in pterygium and normal conjunctival tissue.ResultsWe identified 2,949 dysregulated m6A peaks in pterygium tissue, of which 2,145 were significantly upregulated and 804 were significantly downregulated. The altered m6A peak of genes were found to play a key role in the Hippo signaling pathway and endocytosis. Joint analyses of MeRIP-seq and RNA-seq data identified 72 hypermethylated m6A peaks and 15 hypomethylated m6A peaks in mRNA. After analyzing the differentially methylated m6A peaks and synchronously differentially expressed genes, we searched the Gene Expression Omnibus database and identified five genes related to the development of pterygium (DSP, MXRA5, ARHGAP35, TMEM43, and OLFML2A).ConclusionOur research shows that m6A modification plays an important role in the development of pterygium and can be used as a potential new target for the treatment of pterygium in the future.

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“…Interestingly, in early 1970s several groups showed that also RNA can be methylated (especially N6-methyl-adenosine), but the roles of this methylation are largely unknown and the identification of writers of this marker began very recently [139]. Since RNA methylation is out of scope of this review, readers can find more information in recent reviews [140,141]. Moreover, historic details can be found in recently published paper in IJMS describing timeline of epigenetic discoveries [142].…”

Section: Discussionmentioning

confidence: 99%

DNA Methylation in Solid Tumors: Functions and Methods of Detection

Martisova

Holcakova

Izadi

et al. 2021

IJMS

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DNA methylation, i.e., addition of methyl group to 5′-carbon of cytosine residues in CpG dinucleotides, is an important epigenetic modification regulating gene expression, and thus implied in many cellular processes. Deregulation of DNA methylation is strongly associated with onset of various diseases, including cancer. Here, we review how DNA methylation affects carcinogenesis process and give examples of solid tumors where aberrant DNA methylation is often present. We explain principles of methods developed for DNA methylation analysis at both single gene and whole genome level, based on (i) sodium bisulfite conversion, (ii) methylation-sensitive restriction enzymes, and (iii) interactions of 5-methylcytosine (5mC) with methyl-binding proteins or antibodies against 5mC. In addition to standard methods, we describe recent advances in next generation sequencing technologies applied to DNA methylation analysis, as well as in development of biosensors that represent their cheaper and faster alternatives. Most importantly, we highlight not only advantages, but also disadvantages and challenges of each method.

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Principles of RNA methylation and their implications for biology and medicine

Cited by 89 publications

References 202 publications

Clinical and Prognostic Pan-Cancer Analysis of N6-Methyladenosine Regulators in Two Types of Hematological Malignancies: A Retrospective Study Based on TCGA and GTEx Databases

Clinical and Prognostic Pan-Cancer Analysis of N6-Methyladenosine Regulators in Two Types of Hematological Malignancies: A Retrospective Study Based on TCGA and GTEx Databases

Comprehensive Analysis of the Transcriptome-Wide m6A Methylome in Pterygium by MeRIP Sequencing

DNA Methylation in Solid Tumors: Functions and Methods of Detection

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