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mRNA methylation by NSUN2 in cell proliferation

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Methylation is a prevalent post‐transcriptional modification that occurs in almost all RNA species. NSUN2, a nucleolar RNA methyltransferase, has been shown to methylate mRNAs encoding factors that control cell division and growth arrest, thereby affecting their stability and/or translation. Here, the author summarizes the recent progress in understanding NSUN2‐mediated mRNA methylation and its implications in cell proliferation and senescence. WIREs RNA 2016, 7:838–842. doi: 10.1002/wrna.1380 This article is categorized under: RNA Structure and Dynamics > RNA Structure, Dynamics, and Chemistry Translation > Translation Regulation RNA Turnover and Surveillance > Regulation of RNA Stability
Mechanisms whereby NSUN2 promotes cell proliferation. NSUN2 plays important roles to enable the correct assembly of the mitotic spindle and the nucleolar RNA‐processing machinery components including NuSAP, NPM1, and nucleolin. By methylating the 3′UTR of CDK1 mRNA and the 5′UTR of p27 mRNA, NSUN2 enhances the translation of CDK1 but represses the translation of p27. Methylation at m5C in the 5′UTR, CR, and 3′UTR of CDK1 and p27 mRNAs are indicated.
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NSUN2 regulates replicative senescence and stress‐induced premature senescence by methylating mRNAs encoding senescence‐regulatory factors. In replicative senescence, NSUN2 enhances the translation of CDK1 mRNA and represses the translation of p27 mRNA by methylating the 3′UTR of CDK1 mRNA and the 5′UTR of p27 mRNA. In stress‐induced senescence, NSUN2 methylates the 5′UTR, CR, and 3′UTR of SHC mRNA, as well as the 3′UTR of TP53 and p16 mRNAs, enhances production of TP53 and SHC, and stabilizes the p16 mRNA. The methylated forms (m5C, m6A, or unidentified methylation form [indicated as ‘Met’]) and the locations of the modifications are indicated.
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RNA Structure and Dynamics > RNA Structure, Dynamics, and Chemistry
RNA Turnover and Surveillance > Regulation of RNA Stability
Translation > Translation Regulation

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