Mechanism of N6-methyladenosine modification and its emerging role in cancer

被引：36
作者：
Zhang, Sicong [1 ]
机构：
[1] Rockefeller Univ, Lab Biochem & Mol Biol, 1230 York Ave,Box 166, New York, NY 10065 USA
来源：
PHARMACOLOGY & THERAPEUTICS | 2018年 / 189卷
关键词：
N-6-methyladenosine; m(6)A methylation; Epitranscriptomics; Methyltransferase; Demethylase; Cancer; MESSENGER-RNA METHYLATION; SINGLE-NUCLEOTIDE-RESOLUTION; NUCLEAR-RNA; M(6)A RNA; BINDING-PROTEIN; HETEROGENEOUS NUCLEAR; ADENOSINE RESIDUES; SEX DETERMINATION; STRUCTURAL BASIS; SELF-RENEWAL;
D O I：
10.1016/j.pharmthera.2018.04.011
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
N-6-methyladenosine (m(6)A), the most prevalent internal methylation in messenger RNA (mRNA) that is deposited by m(6)A methyltransferases, removed by m(6)A demethylases and recognized by different RNA binding proteins, distinguishes the transcripts through multilayer interactions with mRNA processing, export, degradation and translation machineries. m(6)A plays an important role in regulation of gene expression for fundamental cellular processes and diverse physiological functions. Aberrant m(6)A decorations lead to cancer but also have the potential to yield new therapies. This review outlines the evolution of the m(6)A field, formation of key concepts, important open questions and also discusses the molecular basis of mRNA m(6)A modification and its effect in cancer, highlighting the potential of demethylase as a therapeutic target for cancer treatment. (C) 2018 Elsevier Inc. All rights reserved.
引用
收藏
页码：173 / 183
页数：11
相关论文
共 129 条
[1]   Coordination of m6A mRNA Methylation and Gene Transcription by ZFP217 Regulates Pluripotency and Reprogramming [J].
Aguilo, Francesca ;
Zhang, Fan ;
Sancho, Ana ;
Fidalgo, Miguel ;
Di Cecilia, Serena ;
Vashisht, Ajay ;
Lee, Dung-Fang ;
Chen, Chih-Hung ;
Rengasamy, Madhumitha ;
Andino, Blanca ;
Jahouh, Farid ;
Roman, Angel ;
Krig, Sheryl R. ;
Wang, Rong ;
Zhang, Weijia ;
Wohlschlegel, James A. ;
Wang, Jianlong ;
Walsh, Martin J. .
CELL STEM CELL, 2015, 17 (06) :689-704
[2]   N6-methyladenosine marks primary microRNAs for processing [J].
Alarcon, Claudio R. ;
Lee, Hyeseung ;
Goodarzi, Hani ;
Halberg, Nils ;
Tavazoie, Sohail F. .
NATURE, 2015, 519 (7544) :482-+
[3]   Promoter-bound METTL3 maintains myeloid leukaemia by m6A-dependent translation control [J].
Barbieri, Isaia ;
Tzelepis, Konstantinos ;
Pandolfini, Luca ;
Shi, Junwei ;
Millan-Zambrano, Gonzalo ;
Robson, Samuel C. ;
Aspris, Demetrios ;
Migliori, Valentina ;
Bannister, Andrew J. ;
Han, Namshik ;
De Braekeleer, Etienne ;
Ponstingl, Hannes ;
Hendrick, Alan ;
Vakoc, Christopher R. ;
Vassiliou, George S. ;
Kouzarides, Tony .
NATURE, 2017, 552 (7683) :126-+
[4]   N6-methyladenosine demethylase FTO targets pre-mRNAs and regulates alternative splicing and 3'-end processing [J].
Bartosovic, Marek ;
Molares, Helena Covelo ;
Gregorova, Pavlina ;
Hrossova, Dominika ;
Kudla, Grzegorz ;
Vanacova, Stepanka .
NUCLEIC ACIDS RESEARCH, 2017, 45 (19) :11356-11370
[5]  
Bartzatt Ronald, 2012, Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, V11, P151
[6]   RNA editing by adenosine deaminases that act on RNA [J].
Bass, BL .
ANNUAL REVIEW OF BIOCHEMISTRY, 2002, 71 :817-846
[7]   m6A RNA Modification Controls Cell Fate Transition in Mammalian Embryonic Stem Cells [J].
Batista, Pedro J. ;
Molinie, Benoit ;
Wang, Jinkai ;
Qu, Kun ;
Zhang, Jiajing ;
Li, Lingjie ;
Bouley, Donna M. ;
Lujan, Ernesto ;
Haddad, Bahareh ;
Daneshvar, Kaveh ;
Carter, Ava C. ;
Flynn, Ryan A. ;
Zhou, Chan ;
Lim, Kok-Seong ;
Dedon, Peter ;
Wernig, Marius ;
Mullen, Alan C. ;
Xing, Yi ;
Giallourakis, Cosmas C. ;
Chang, Howard Y. .
CELL STEM CELL, 2014, 15 (06) :707-719
[8]  
Bokar JA, 1997, RNA, V3, P1233
[9]  
BOKAR JA, 1994, J BIOL CHEM, V269, P17697
[10]   Methyltransferase-like protein 16 binds the 3′-terminal triple helix of MALAT1 long noncoding RNA [J].
Brown, Jessica A. ;
Kinzig, Charles G. ;
DeGregorio, Suzanne J. ;
Steitz, Joan A. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2016, 113 (49) :14013-14018
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