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Transfer RNA demethylase ALKBH3 promotes cancer progression via induction of tRNA-derived small RNAs.
Chen, Zhuojia; Qi, Meijie; Shen, Bin; Luo, Guanzheng; Wu, Yingmin; Li, Jiexin; Lu, Zhike; Zheng, Zhong; Dai, Qing; Wang, Hongsheng.
Afiliación
  • Chen Z; Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.
  • Qi M; Department of Chemistry, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.
  • Shen B; State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 211166, China.
  • Luo G; State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 211166, China.
  • Wu Y; Department of Chemistry, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.
  • Li J; School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, China.
  • Lu Z; Department of Microbial and Biochemical Pharmacy, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
  • Zheng Z; Department of Microbial and Biochemical Pharmacy, Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
  • Dai Q; Department of Chemistry, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.
  • Wang H; Department of Chemistry, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA.
Nucleic Acids Res ; 47(5): 2533-2545, 2019 03 18.
Article en En | MEDLINE | ID: mdl-30541109
ABSTRACT
Transfer RNA is heavily modified and plays a central role in protein synthesis and cellular functions. Here we demonstrate that ALKBH3 is a 1-methyladenosine (m1A) and 3-methylcytidine (m3C) demethylase of tRNA. ALKBH3 can promote cancer cell proliferation, migration and invasion. In vivo study confirms the regulation effects of ALKBH3 on growth of tumor xenograft. The m1A demethylated tRNA is more sensitive to angiogenin (ANG) cleavage, followed by generating tRNA-derived small RNAs (tDRs) around the anticodon regions. tDRs are conserved among species, which strengthen the ribosome assembly and prevent apoptosis triggered by cytochrome c (Cyt c). Our discovery opens a potential and novel paradigm of tRNA demethylase, which regulates biological functions via generation of tDRs.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: ARN de Transferencia / Proliferación Celular / Dioxigenasa Dependiente de Alfa-Cetoglutarato, Homólogo 3 de AlkB / Neoplasias Límite: Animals / Humans Idioma: En Revista: Nucleic Acids Res Año: 2019 Tipo del documento: Article País de afiliación: China
Texto completo
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: ARN de Transferencia / Proliferación Celular / Dioxigenasa Dependiente de Alfa-Cetoglutarato, Homólogo 3 de AlkB / Neoplasias Límite: Animals / Humans Idioma: En Revista: Nucleic Acids Res Año: 2019 Tipo del documento: Article País de afiliación: China