Chemical Modifications in the Life of an mRNA Transcript.
Sigrid Nachtergaele,Chuan He +1 more
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TL;DR: Investigations over the past eight years of chemical modifications on messenger RNA have revealed a new level of posttranscriptional gene regulation in eukaryotes, and m6A methylation provides a rapid mechanism for coordinated transcriptome processing and turnover that is important in embryonic development and cell differentiation.
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Abstract: Investigations over the past eight years of chemical modifications on messenger RNA (mRNA) have revealed a new level of posttranscriptional gene regulation in eukaryotes Rapid progress in our understanding of these modifications, particularly, N6-methyladenosine (m6A), has revealed their roles throughout the life cycle of an mRNA transcript m6A methylation provides a rapid mechanism for coordinated transcriptome processing and turnover that is important in embryonic development and cell differentiation In response to cellular signals, m6A can also regulate the translation of specific pools of transcripts These mechanisms can be hijacked in human diseases, including numerous cancers and viral infection Beyond m6A, many other mRNA modifications have been mapped in the transcriptome, but much less is known about their biological functions As methods continue to be developed, we will be able to study these modifications both more broadly and in greater depth, which will likely reveal a wealth of new RNA biology
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Citations
The Critical Role of RNA m6A Methylation in Cancer
TL;DR: Screening for selective and potent RNA methyltransferase, demethylase, or m6A-binding protein inhibitors may lead to compounds suitable for future clinical trials in cancer patients.
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The emerging role of RNA modifications in the regulation of mRNA stability
Sung Ho Boo,Yoon Ki Kim +1 more
TL;DR: Current understanding of the molecular mechanisms underlying the regulation of mammalian mRNA stability by various RNA modifications is discussed, including small chemical groups added to any of the four nucleotide groups that make up an RNA molecule.
Molecular Mechanisms Driving mRNA Degradation by m6A Modification
TL;DR: The current understanding of the dynamic regulation of m6A-mediated mRNA decay through the crosstalk between m 6A (or YTHDF2) and other cellular factors is described.
374
m 6 A RNA methyltransferases METTL3/14 regulate immune responses to anti-PD-1 therapy.
TL;DR: These findings uncover a new awareness of the function of RNA methylation in adaptive immunity and provide METTL3 and METTL14 as potential therapeutic targets in anticancer immunotherapy.
321
The m6A epitranscriptome: transcriptome plasticity in brain development and function
Ido Livneh,Sharon Moshitch-Moshkovitz,Sharon Moshitch-Moshkovitz,Ninette Amariglio,Ninette Amariglio,Gideon Rechavi,Gideon Rechavi,Dan Dominissini,Dan Dominissini +8 more
TL;DR: The mechanisms that are involved in the writing, erasing and reading of N6-methyladenosine, the most prevalent internal mRNA modification, and the emerging roles played by N 6-methyl adenosine in the nervous system are described.
261
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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.
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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.
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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.
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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
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Regulation of Translation Initiation in Eukaryotes: Mechanisms and Biological Targets
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