Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.isci.2020.100968
Title: The SUMOylated METTL8 Induces R-loop and Tumorigenesis via m3C
Authors: Zhang, L.-H.
Zhang, X.-Y.
Hu, T.
Chen, X.-Y.
Li, J.-J.
Raida, M. 
Sun, N.
Luo, Y.
Gao, X.
Keywords: Biological Sciences
Cancer
Molecular Biology
Molecular Mechanism of Gene Regulation
Molecular Structure
Issue Date: 2020
Publisher: Elsevier Inc.
Citation: Zhang, L.-H., Zhang, X.-Y., Hu, T., Chen, X.-Y., Li, J.-J., Raida, M., Sun, N., Luo, Y., Gao, X. (2020). The SUMOylated METTL8 Induces R-loop and Tumorigenesis via m3C. iScience 23 (3) : 100968. ScholarBank@NUS Repository. https://doi.org/10.1016/j.isci.2020.100968
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
Abstract: Biological Sciences; Molecular Biology; Molecular Structure; Molecular Mechanism of Gene Regulation; Cancer © 2020 The Author(s)R-loops, three-stranded DNA-DNA:RNA hybrid structures, are best known for their deleterious effects on genome stability. The regulatory factors of this fundamental genetic structure remain unclear. Here, we reveal an epigenetic factor that controls R-loop stability. METTL8, a member of the methyltransferase-like protein family that methylates 3-methylcytidine (m3C), is a key factor in the R-loop regulating methyltransferase complex. Biochemical studies show that METTL8 forms a large SUMOylated nuclear RNA-binding protein complex (∼0.8 mega daltons) that contains well-reported R-loop related factors. Genetic ablation of METTL8 results in an overall reduction of R-loops in cells. Interaction assays indicated METTL8 binds to RNAs and is responsible for R-loop stability on selected gene regions. Our results demonstrate that the SUMOylated METTL8 promotes tumorigenesis by affecting genetic organization primarily in, or in close proximity to, the nucleolus and impacts the formation of regulatory R-loops through its methyltransferase activity on m3C. © 2020 The Author(s)
Source Title: iScience
URI: https://scholarbank.nus.edu.sg/handle/10635/198928
ISSN: 2589-0042
DOI: 10.1016/j.isci.2020.100968
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International
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