RNA m6A Modification in Cancers: Molecular Mechanisms and Potential Clinical Applications
Chang Gu,Xin Shi,Chenyang Dai,Feng Shen,Gaetano Rocco,Jiafei Chen,Zhengyu Huang,Chunji Chen,Chuan He,Tao Huang,Chang Chen +10 more
TLDR
The underlying mechanisms of m6A modifications in tumorigenesis are emphasized and the potential m 6A regulators-associated therapeutic targets for tumor therapy are introduced.Abstract:
N6-Methyladenosine (m6A) RNA modification brings a new dawn for RNA modification researches in recent years. This posttranscriptional RNA modification is dynamic and reversible, and is regulated by methylases ("writers"), demethylases ("erasers"), and proteins that preferentially recognize m6A modifications ("readers"). The change of RNA m6A modification regulates RNA metabolism in eucaryon, including translation, splicing, exporting, decay, and processing. Thereby the dysregulation of m6A may lead to tumorigenesis and progression. Given the tumorigenic role of abnormal m6A expression, m6A regulators may function as potential clinical therapeutic targets for cancers. In this review, we emphasize on the underlying mechanisms of m6A modifications in tumorigenesis and further introduce the potential m6A regulators-associated therapeutic targets for tumor therapy.read more
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References
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Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq
Dan Dominissini,Sharon Moshitch-Moshkovitz,Schraga Schwartz,Schraga Schwartz,Mali Salmon-Divon,Lior Ungar,Sivan Osenberg,Sivan Osenberg,Karen Cesarkas,Jasmine Jacob-Hirsch,Ninette Amariglio,Martin Kupiec,Rotem Sorek,Gideon Rechavi,Gideon Rechavi +14 more
TL;DR: The findings suggest that RNA decoration by m6A has a fundamental role in regulation of gene expression, and a subset of stimulus-dependent, dynamically modulated sites is identified.
Journal ArticleDOI
Comprehensive Analysis of mRNA Methylation Reveals Enrichment in 3′ UTRs and near Stop Codons
Kate D. Meyer,Yogesh Saletore,Paul Zumbo,Olivier Elemento,Christopher E. Mason,Samie R. Jaffrey +5 more
TL;DR: A method is presented for transcriptome-wide m(6)A localization, which combines m( 6)A-specific methylated RNA immunoprecipitation with next-generation sequencing (MeRIP-Seq) and reveals insights into the epigenetic regulation of the mammalian transcriptome.
Journal ArticleDOI
N6-methyladenosine-dependent regulation of messenger RNA stability
Xiao Wang,Zhike Lu,Adrian Gomez,Gary C. Hon,Yanan Yue,Dali Han,Ye Fu,Marc Parisien,Qing Dai,Guifang Jia,Bing Ren,Tao Pan,Chuan He +12 more
TL;DR: It is shown that m6A is selectively recognized by the human YTH domain family 2 (YTHDF2) ‘reader’ protein to regulate mRNA degradation and established the role of YTH DF2 in RNA metabolism, showing that binding of Y THDF2 results in the localization of bound mRNA from the translatable pool to mRNA decay sites, such as processing bodies.
Journal ArticleDOI
N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO.
Guifang Jia,Ye Fu,Xu Zhao,Xu Zhao,Qing Dai,Guanqun Zheng,Ying Yang,Ying Yang,Chengqi Yi,Tomas Lindahl,Tao Pan,Yun-Gui Yang,Yun-Gui Yang,Chuan He +13 more
TL;DR: FTO exhibits efficient oxidative demethylation activity of abundant N6-methyladenosine (m6A) residues in RNA in vitro, and it is shown that FTO partially colocalizes with nuclear speckles, supporting m6A in nuclear RNA as a physiological substrate of FTO.
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ALKBH5 Is a Mammalian RNA Demethylase that Impacts RNA Metabolism and Mouse Fertility
Guanqun Zheng,John Arne Dahl,Yamei Niu,Peter Fedorcsak,Chun-Min Huang,Charles J. Li,Cathrine Broberg Vågbø,Yue Shi,Yue Shi,Wen-Ling Wang,Wen-Ling Wang,Shuhui Song,Zhike Lu,Ralph P. G. Bosmans,Qing Dai,Ya-Juan Hao,Ya-Juan Hao,Xin Yang,Xin Yang,Wenming Zhao,Wei-Min Tong,Xiu-Jie Wang,Florian Bogdan,Kari Furu,Ye Fu,Guifang Jia,Xu Zhao,Xu Zhao,Jun Liu,Hans E. Krokan,Arne Klungland,Yun-Gui Yang,Yun-Gui Yang,Chuan He +33 more
TL;DR: The discovery of ALKBH5 as another mammalian demethylase that oxidatively reverses m(6)A in mRNA in vitro and in vivo strongly suggests that the reversible m( 6)A modification has fundamental and broad functions in mammalian cells.