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Differential m6A, m6Am, and m1A Demethylation Mediated by FTO in the Cell Nucleus and Cytoplasm.
Wei, Jiangbo; Liu, Fange; Lu, Zhike; Fei, Qili; Ai, Yuxi; He, P Cody; Shi, Hailing; Cui, Xiaolong; Su, Rui; Klungland, Arne; Jia, Guifang; Chen, Jianjun; He, Chuan.
Afiliação
  • Wei J; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57 Street, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, 929 East 57 Street, Chicago, IL 60637, USA.
  • Liu F; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57 Street, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, 929 East 57 Street, Chicago, IL 60637, USA.
  • Lu Z; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57 Street, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, 929 East 57 Street, Chicago, IL 60637, USA; Institute
  • Fei Q; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57 Street, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, 929 East 57 Street, Chicago, IL 60637, USA.
  • Ai Y; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57 Street, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, 929 East 57 Street, Chicago, IL 60637, USA.
  • He PC; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57 Street, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, 929 East 57 Street, Chicago, IL 60637, USA.
  • Shi H; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57 Street, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, 929 East 57 Street, Chicago, IL 60637, USA.
  • Cui X; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57 Street, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, 929 East 57 Street, Chicago, IL 60637, USA.
  • Su R; Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
  • Klungland A; Institute of Medical Microbiology, Oslo University Hospital, Rikshospitalet, Norway Institute of Basic Medical Sciences, University of Oslo, PO Box 1018 Blindern, 0315 Oslo, Norway.
  • Jia G; Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
  • Chen J; Department of Systems Biology, Beckman Research Institute of City of Hope, Monrovia, CA 91016, USA.
  • He C; Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, 929 East 57 Street, Chicago, IL 60637, USA; Howard Hughes Medical Institute, The University of Chicago, 929 East 57 Street, Chicago, IL 60637, USA. Electronic
Mol Cell ; 71(6): 973-985.e5, 2018 09 20.
Article em En | MEDLINE | ID: mdl-30197295
ABSTRACT
FTO, the first RNA demethylase discovered, mediates the demethylation of internal N6-methyladenosine (m6A) and N6, 2-O-dimethyladenosine (m6Am) at the +1 position from the 5' cap in mRNA. Here we demonstrate that the cellular distribution of FTO is distinct among different cell lines, affecting the access of FTO to different RNA substrates. We find that FTO binds multiple RNA species, including mRNA, snRNA, and tRNA, and can demethylate internal m6A and cap m6Am in mRNA, internal m6A in U6 RNA, internal and cap m6Am in snRNAs, and N1-methyladenosine (m1A) in tRNA. FTO-mediated demethylation has a greater effect on the transcript levels of mRNAs possessing internal m6A than the ones with cap m6Am in the tested cells. We also show that FTO can directly repress translation by catalyzing m1A tRNA demethylation. Collectively, FTO-mediated RNA demethylation occurs to m6A and m6Am in mRNA and snRNA as well as m1A in tRNA.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Adenosina / Dioxigenase FTO Dependente de alfa-Cetoglutarato Limite: Animals / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Adenosina / Dioxigenase FTO Dependente de alfa-Cetoglutarato Limite: Animals / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article