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Detailed resume of rna m^(6)A demethylases

Acta Pharmaceutica Sinica B 2022年第5期12卷 2193-2205页

作者： Dandan Shen Bo Wang Ya Gao Lijuan Zhao Yaping Bi Jinge Zhang Ning Wang Huiqin Kang Jingru Pang Ying Liu Luping Pang Zhe-Sheng Chen Yi-Chao Zheng Hong-Min Liu Key Laboratory of Advanced Drug Preparation Technologies Ministry of Education of ChinaCollaborative Innovation Center of New Drug Research and Safety EvaluationZhengzhou UniversityZhengzhou 450052China Key Laboratory of Henan Province for Drug Quality and Evaluation Institute of Drug Discovery and DevelopmentSchool of Pharmaceutical SciencesZhengzhou UniversityZhengzhou 450052China State Key Laboratory of Esophageal Cancer Prevention&Treatment Academy of Medical SciencesZhengzhou UniversityZhengzhou 450052China Department of Pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s UniversityQueensNY 11439USA The School of Chinese Medicine The University of Hong KongPokfulamHong KongChina

N6-Methyladenosine(m^(6)A) is the most abundant internal modification in eukaryotic mrna,playing critical role in various bioprocesses. Like other epigenetic modifications, m^(6)A modification can be catalyzed by the methyltransferase complex and erased dynamically to maintain cells homeostasis. Up to now, only two m^(6)A demethylases have been reported, fat mass and obesity-associated protein(FTO)and alkylation protein AlkB homolog 5(ALKBH5), involving in a wide range of mrna biological progress, including mrna shearing, export, metabolism and stability. Furthermore, they participate in many significantly biological signaling pathway, and contribute to the progress and development of cancer along with other diseases. In this review, we focus on the studies about structure, inhibitors development and biological function of FTO and ALKBH5.

关键词： FTO ALKBH5 rna demethylation Diseases Inhibitors Screening

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维普期刊数据库

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YTH Domain： A Family of N^6-methyladenosine (m^6A) Readers

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Genomics, Proteomics & Bioinformatics 2018年第2期16卷 99-107页

作者： Shanhui Liao Hongbin Sun Chao Xu Heifei National Laboratory for Physical Sciences at the Microscale and Technology of China Hefei 230027 China School of Food and Biological Engineering Zhengzhou University of Light Industry Zhengzhou 450002 China CAS Key Laboratory of Structural Biology University of Science and Technology of China Hefei 230027 China

Like protein and DNA, different types of rna molecules undergo various modifications. Accumulating evidence suggests that these rna modifications serve as sophisticated codes to mediate rna behaviors and many important biological functions. N^6-methyladenosine （m^6A） is the most abundant internal rna modification found in a variety of eukaryotic rnas, including but not limited to mrnas, trnas, rrnas, and long non-coding rnas （lncrnas）. In mammalian cells, m^6A can be incorporated by a methyltransferase complex and removed by demethy- lases, which ensures that the m^6A modification is reversible and dynamic. Moreover, m^6A is recognized by the YT521-B homology （YTH） domain-containing proteins, which subsequently direct different complexes to regulate rna signaling pathways, such as rna metabolism, rna splicing, rna folding, and protein translation. Herein, we summarize the recent progresses made in understanding the molecular mechanisms underlying the m^6A recognition by YTH domaincontaining proteins, which would shed new light on m^6A-specific recognition and provide clues to the future identification of reader proteins of many other rna modifications.

关键词： rna modification rna methylation rna demethylation YT521-B homology Epitranscriptome

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维普期刊数据库

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Identification of Flavin Mononucleotide as a Cell-Active Artificial N6-Methyladenosine rna Demethylase

Identification of Flavin Mononucleotide as a Cell-Active Art...

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中国生物化学与分子生物学会2019年全国学术会议暨学会...

作者： Li-Jun Xie Xiao-Ti Yang Ming Wang Liang Cheng Beijing National Laboratory for Molecular Sciences (BNLMS) Institute of Chemistry Chinese Academy of Sciences

N-Methyladenosine(mA) 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 mA residues in mrna. Herein, the first identification of a small-molecule modulator that functions as an artificial mA demethylase is reported. Flavin mononucleotide(FMN), the metabolite produced by riboflavin kinase, mediates substantial photochemical demethylation of mA residues of rna in live cells. This study provides a new perspective to the understanding of demethylation of m A residues in mrna and sheds light on the development of powerful small molecules as rna demethylases and new probes for use in rna biology.

关键词： artificial enzymes flavin mononucleotide m6A rna rna demethylase rna demethylation

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