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The SUMOylated METTL8 Induces R-loop and Tumorigenesis via m3C.
Zhang, Li-Hong; Zhang, Xue-Yun; Hu, Tao; Chen, Xin-Yun; Li, Jing-Jia; Raida, Manfred; Sun, Ning; Luo, Yan; Gao, Xiang.
Afiliación
  • Zhang LH; Department of Biochemistry and Cancer Institute of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China; Key Laboratory of Cancer Prevention and Intervention of China National Ministry of Education, Hangzhou 310009, China.
  • Zhang XY; Department of Biochemistry and Cancer Institute of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China; Key Laboratory of Cancer Prevention and Intervention of China National Ministry of Education, Hangzhou 310009, China.
  • Hu T; Department of Spine Surgery, Shanghai East Hospital, Tongji University, Shanghai 200092, China.
  • Chen XY; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.
  • Li JJ; Department of Biochemistry and Cancer Institute of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China; Key Laboratory of Cancer Prevention and Intervention of China National Ministry of Education, Hangzhou 310009, China.
  • Raida M; Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore.
  • Sun N; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.
  • Luo Y; Department of Biochemistry and Cancer Institute of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China; Key Laboratory of Cancer Prevention and Intervention of China National Ministry of Education, Hangzhou 310009, China. Electronic address: luoyan2011@zju.
  • Gao X; Department of Biochemistry and Cancer Institute of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China; Key Laboratory of Cancer Prevention and Intervention of China National Ministry of Education, Hangzhou 310009, China. Electronic address: shawngao@zju.ed
iScience ; 23(3): 100968, 2020 Mar 27.
Article en En | MEDLINE | ID: mdl-32199293
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: IScience Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: IScience Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos