Internal m7G methylation: A novel epitranscriptomic contributor in brain development and diseases

Xia, Xiaohuan; Wang, Yi; Zheng, Jialin

doi:10.1016/j.omtn.2023.01.003

Cited by 30 publications

(26 citation statements)

References 132 publications

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“…Growing evidence indicates a critical role of m 7 G in the development of human disease, especially cancer ( Wang et al, 2023 ; Xia et al, 2023 ). The m 7 G modification can occur in miRNAs, and aberrant m 7 G levels are closely associated with tumorigenesis and progression via regulation of the expression of downstream targets, such as multiple oncogenes and tumor suppressor genes ( Ma et al, 2021a ; Luo et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

A novel serum m7G-harboring microRNA signature for cancer detection

Chen,

Xie,

et al. 2024

Front. Genet.

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Background: Emerging evidence points to the exceptional importance and value of m7G alteration in the diagnosis and prognosis of cancers. Nonetheless, a biomarker for precise screening of various cancer types has not yet been developed based on serum m7G-harboring miRNAs.Methods: A total of 20,702 serum samples, covering 12 cancer types and consisting of 7,768 cancer samples and 12,934 cancer-free samples were used in this study. A m7G target miRNA diagnostic signature (m7G-miRDS) was established through the least absolute shrinkage and selection operator (LASSO) analyses in a training dataset (n = 10,351), and validated in a validation dataset (n = 10,351).Results: The m7G-miRDS model, a 12 m7G-target-miRNAs signature, demonstrated high accuracy and was qualified for cancer detection. In the training and validation cohort, the area under the curve (AUC) reached 0.974 (95% CI 0.971–0.977) and 0.972 (95% CI 0.969–0.975), respectively. The m7G-miRDS showed superior sensitivity in each cancer type and had a satisfactory AUC in identifying bladder cancer, lung cancer and esophageal cancer. Additionally, the diagnostic performance of m7G-miRDS was not interfered by the gender, age and benign disease.Conclusion: Our results greatly extended the value of serum circulating miRNAs and m7G in cancer detection, and provided a new direction and strategy for the development of novel biomarkers with high accuracy, low cost and less invasiveness for mass cancer screening, such as ncRNA modification.

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Section: Discussionmentioning

confidence: 99%

A novel serum m7G-harboring microRNA signature for cancer detection

Chen,

Xie,

et al. 2024

Front. Genet.

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“…The frequency of gain was higher than loss for eight genes, while the frequency of gain for 21 genes was lower (Figure 2D). The distribution of these genes occurred on chromosomes 2, 3,5,6,8,9,10,11,12,15,17,21,22, and X can be observed in Figure 2E.…”

Section: Characteristics At the Molecular Level Of Regulators Of M7g ...mentioning

confidence: 94%

Integrative analyses reveal biological function and prognostic role of m7G methylation regulators in high-grade glioma

Li,

et al. 2023

Aging

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Based on 29 m7G regulators, glioma patients were categorized into three groups using data from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) datasets. Distinct characteristics were observed in immune cell infiltration, functional enrichment, and clinical prognosis for every glioma subtype. Analyzing the differentially expressed genes (DEGs) confirmed the distinction among the three m7G clusters. A predictive tool for overall survival (OS) in high-grade glioma patients was developed and confirmed, consisting of 13 m7G regulators forming a prognostic signature. Elevated m7G levels were found to be associated with increased tumor mutation burden and immune activation, indicating a tumor microenvironment characterized by inflammation and a lower overall survival rate. In contrast, reduced m7G scores were linked to a deficiency in immune infiltration, a low burden of mutations, and a non-inflamed phenotype, suggesting a more positive clinical outlook. Additionally, the m7G risk scores were found to impact chemotherapy sensitivity. The m7G predictive pattern shows potential as a marker for the overall survival of patients with high-grade glioma. By significantly improving our comprehension of the functional role of m7G regulators in the advancement of glioma and their impact on clinical results, this study offers valuable perspectives for precision therapy in the management of high-grade glioma.

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“…The development of NGS technologies has promoted m 7 G description on the whole transcriptome. , m 7 G-miCLIP-seq combined ultraviolet (UV) cross-linking and anti-m 7 G antibody for immunoprecipitation enrichment to profile m 7 G map in individual-nucleotide resolution. m 7 G-seq and m 7 G-MaP-seq utilized sodium borohydride (NaBH 4 ) treatment to selectively convert the internal m 7 G into abasic sites, inducing mismatch and achieving base resolution.…”

Section: Sequencing Methods and Regulators Of Rna Methylationmentioning

confidence: 99%

“…Available evidence demonstrates that m 7 G also plays a regulatory role in neurodevelopment and stem cell development 19 (Table S3). tRNA m 7 G46 impairment due to mutant WDR4 causes a distinct form of microcephalic primordial dwarfism.…”

Section: Role Of Rna M 7 G In Developmentmentioning

confidence: 99%

Emerging Roles of RNA Methylation in Development

Wang,

Gao,

Yang

2023

Acc. Chem. Res.

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Conspectus More than 170 different types of chemical modifications have been identified on diverse types of RNA, collectively known as the epitranscriptome. Among them, N 6-methyladenine (m6A), 5-methylcytosine (m5C), N 1-methyladenine (m1A), and N 7-methylguanosine (m7G) as the ubiquitous post-transcriptional modification are widely involved in regulating the metabolic processes such as RNA degradation, translation, stability, and export, mediating important physiological and pathological processes such as stress regulation, immune response, development, and tumorigenesis. Recently, the regulatory role of RNA modification during developmental processes is getting more attention. Therefore, the development of low-input even single-cell and high-resolution sequencing technologies is crucial for the exploration of the regulatory roles of RNA modifications in these important biological events of trace samples. This account focuses on the roles of RNA modifications in various developmental processes. We describe the distribution characteristics of various RNA modifications, catalytic enzymes, binding proteins, and the development of sequencing technologies. RNA modification is dynamically reversible, which can be catalyzed by methyltransferases and eliminated by demethylases. RNA m6A is the most abundant post-transcriptional modification on eukaryote mRNA, which is mainly concentrated near the stop codon, and involves in RNA metabolism regulation. RNA m5C, another most studied RNA modification, has been identified in a various of organisms and RNA species, mainly enriched in the regions downstream of translation initiation sites and broadly distributes across the whole coding sequence (CDS) in mammalian mRNAs. RNA m1A, with a lower abundance than m6A, is widely distributed in various RNA types, mainly locates in the 5′ untranslated region (5′UTR) of mRNA and regulates translation. RNA m7G, one of the most common RNA modifications in eukaryotes, has been identified at cap regions and internal positions of RNAs and recently gained considerable attention. Thanks to the development of sequencing technology, m6A has been found to regulate the tumorigenic process, including tumor proliferation, invasion, and metastasis by modulating oncogenes and tumor suppressor genes, and affect oocyte maturation and embryonic development through regulating maternal and zygotic genes. m5C related proteins have been identified to participate in embryonic development, plant growth, and neural stem cell differentiation in a m5C dependent manner. m1A also has been revealed to be involved in these developmental processes. m7G dysregulation mainly involves in neurodevelopmental disorders and neurodegenerative diseases. Collectively, we summarized the gradually exhibited roles of RNA methylation during development, and discussed the possibility of RNA modifications as candidate biomarkers and potential therapeutic targets. The technological development is anticipated as the major driving force to expand our knowledge in this field.

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Internal m7G methylation: A novel epitranscriptomic contributor in brain development and diseases

Cited by 30 publications

References 132 publications

A novel serum m7G-harboring microRNA signature for cancer detection

A novel serum m7G-harboring microRNA signature for cancer detection

Integrative analyses reveal biological function and prognostic role of m7G methylation regulators in high-grade glioma

Emerging Roles of RNA Methylation in Development

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