A review on the role of RNA methylation in aging-related diseases

Wei, Hong; Xu, Yuhao; Lin, Li; Li, Yuefeng; Zhu, Xiaolan

doi:10.1016/j.ijbiomac.2023.127769

International Journal of Biological Macromolecules

2024

DOI: 10.1016/j.ijbiomac.2023.127769

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A review on the role of RNA methylation in aging-related diseases

Hong Wei,

Yuhao Xu,

Li Lin

et al.

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2024

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Cited by 2 publications

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RNA m6A methylation regulatory mechanism of resveratrol in premature senescence cells

Zhang,

Zhu,

Zhang

et al. 2024

Food Science & Nutrition

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Resveratrol, a natural compound found in various plants, is known for its anti‐inflammatory, antioxidant, and senescence‐delaying properties. RNA N6‐methyladenosine (m6A) methylation plays a crucial role in oxidative stress and premature cellular senescence processes and is closely associated with age‐related disorders. However, the anti‐premature senescence via RNA m6A methylation mechanism of resveratrol is still not fully understood. In this study, based on premature senescence model of human embryonic lung fibroblasts (HEFs) induced by hydrogen peroxide (H2O2), a widely accepted model of premature senescence caused by oxidative stress, we explored the anti‐aging regulatory effects of resveratrol at the RNA m6A methylation level. Our data suggested that resveratrol significantly delayed premature senescence by increasing cell viability, reducing SA‐β‐gal blue staining rate, ROS levels, and senescence‐associated secretory phenotypes (SASP) expression in HEFs. Meanwhile, resveratrol increased the whole RNA methyltransferases activity and the overall m6A level during senescence. Furthermore, three genes CCND2, E2F1, and GADD45B have been identified as the main ones regulating premature by resveratrol. Specifically, it decreased E2F1, GADD45B RNA m6A methylation level, and increased CCND2 level in premature cells. Our study provided new clues for exploring the mechanism and application of resveratrol in the field of premature aging.

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RNA m6A methylation regulatory mechanism of resveratrol in premature senescence cells

Zhang,

Zhu,

Zhang

et al. 2024

Food Science & Nutrition

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The miR-6240 target gene Igf2bp3 promotes myoblast fusion by enhancing myomaker mRNA stability

Huang,

Wang,

Fan

et al. 2024

Cell Mol Biol Lett

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Background Myoblast fusion plays a crucial role in myogenesis. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) functions as an RNA N6-methyladenosine reader and exerts important roles in various biological processes. While our prior study suggested Igf2bp3 contributes to myogenesis, its molecular regulatory mechanism is largely unclear. Methods Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were used for gene expression analysis. siRNA and CRISPRi technologies were conducted to knockdown the expression of Igf2bp3. CRISPR/Cas9 technology was performed to knockout Igf2bp3. The Igf2bp3 overexpression vector was designed using the pcDNA3.1(+) vector. Immunofluorescence detection was employed for subcellular localization and cell differentiation analysis. Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (EdU) assays were conducted for cell proliferation and fusion detection. The dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were utilized for regulatory mechanism analysis of Igf2bp3. Results The overexpression of Igf2bp3 enhances myoblast fusion while knockdown of Igf2bp3 blocks the formation of myotubes. miR-6240 promotes myoblast proliferation while preventing myoblast differentiation and fusion by targeting the 3′ untranslated rgion (UTR) of Igf2bp3. Notably, the impacts of miR-6240 mimics on myoblast proliferation, differentiation, and fusion can be effectively counteracted by the overexpression of Igf2bp3. Moreover, our findings elucidate a direct interaction between Igf2bp3 and the myoblast fusion factor myomaker (Mymk). Igf2bp3 binds to Mymk to enhance its mRNA stability. This interaction results in increased expression of Mymk and heightened myoblast fusion. Conclusions Our study unveils Igf2bp3 as a novel post-transcriptional regulator of myoblast fusion through the miR-6240/Mymk axis, significantly contributing to our understanding of skeletal muscle development. Graphical Abstract

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A review on the role of RNA methylation in aging-related diseases

Cited by 2 publications

References 221 publications

RNA m6A methylation regulatory mechanism of resveratrol in premature senescence cells

RNA m6A methylation regulatory mechanism of resveratrol in premature senescence cells

The miR-6240 target gene Igf2bp3 promotes myoblast fusion by enhancing myomaker mRNA stability

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