Volume 58, Issue 15
Communication

Identification of Flavin Mononucleotide as a Cell‐Active Artificial N 6‐Methyladenosine RNA Demethylase

Li‐Jun Xie

Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key Laboratory of Molecular Recognition and Function, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190 China

University of Chinese Academy of Sciences, Beijing, 100049 China

These authors contributed equally to this work.

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Xiao‐Ti Yang

BNLMS, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, China

University of Chinese Academy of Sciences, Beijing, 100049 China

These authors contributed equally to this work.

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Rui‐Li Wang

Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key Laboratory of Molecular Recognition and Function, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190 China

University of Chinese Academy of Sciences, Beijing, 100049 China

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Hou‐Ping Cheng

Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key Laboratory of Molecular Recognition and Function, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190 China

University of Chinese Academy of Sciences, Beijing, 100049 China

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Zhi‐Yan Li

Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key Laboratory of Molecular Recognition and Function, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190 China

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Prof. Dr. Li Liu

Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key Laboratory of Molecular Recognition and Function, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190 China

University of Chinese Academy of Sciences, Beijing, 100049 China

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Prof. Dr. Lanqun Mao

BNLMS, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, China

University of Chinese Academy of Sciences, Beijing, 100049 China

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Prof. Dr. Ming Wang

Corresponding Author

E-mail address: mingwang@iccas.ac.cn

BNLMS, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, China

University of Chinese Academy of Sciences, Beijing, 100049 China

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Prof. Dr. Liang Cheng

Corresponding Author

E-mail address: chengl@iccas.ac.cn

Beijing National Laboratory for Molecular Sciences (BNLMS), CAS Key Laboratory of Molecular Recognition and Function, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190 China

Key Lab of Functional Molecular Engineering of Guangdong Province, South China University of Technology), Guangzhou, 510640 China

University of Chinese Academy of Sciences, Beijing, 100049 China

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First published: 12 February 2019
Citations: 8

In memory of Professor Ronald Breslow (1931–2017)

Abstract

N 6‐Methyladenosine (m6A) represents a common and highly dynamic modification in eukaryotic RNA that affects various cellular pathways. Natural dioxygenases such as FTO and ALKBH5 are enzymes that demethylate m6A residues in mRNA. Herein, the first identification of a small‐molecule modulator that functions as an artificial m6A demethylase is reported. Flavin mononucleotide (FMN), the metabolite produced by riboflavin kinase, mediates substantial photochemical demethylation of m6A residues of RNA in live cells. This study provides a new perspective to the understanding of demethylation of m6A residues in mRNA and sheds light on the development of powerful small molecules as RNA demethylases and new probes for use in RNA biology.

Number of times cited according to CrossRef: 8

  • Regioselective synthesis and anticancer evaluation of H 2 O 2 -activable nucleosides , Chemical Communications, 10.1039/D0CC02245D, (2020).
  • Chemical Deprenylation of N6‐Isopentenyladenosine (i6A) RNA, Angewandte Chemie, 10.1002/ange.202003360, 0, 0, (2020).
  • Chemical Deprenylation of N6‐Isopentenyladenosine (i6A) RNA, Angewandte Chemie International Edition, 10.1002/anie.202003360, 0, 0, (2020).
  • Targeted mRNA demethylation using an engineered dCas13b-ALKBH5 fusion protein, Nucleic Acids Research, 10.1093/nar/gkaa269, (2020).
  • Asymmetric polymerase chain reaction and loop-mediated isothermal amplification (AP-LAMP) for ultrasensitive detection of microRNAs, Chinese Chemical Letters, 10.1016/j.cclet.2019.05.003, (2019).
  • A Chemical Photo‐Oxidation of 5‐Methyl Cytidines, Advanced Synthesis & Catalysis, 10.1002/adsc.201900811, 361, 20, (4685-4690), (2019).
  • Visible‐Light Facilitated Fluorescence “Switch‐On” Labelling of 5‐Formylpyrimidine RNA, Advanced Synthesis & Catalysis, 10.1002/adsc.201901032, 361, 23, (5406-5411), (2019).
  • A NaI/H 2 O 2 -Mediated Sulfenylation and Selenylation of Unprotected Uracil and Its Derivatives , Organic Letters, 10.1021/acs.orglett.9b02183, (2019).

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