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
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TLDR
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.Abstract:
N(6)-methyladenosine (m(6)A) is the most prevalent internal (non-cap) modification present in the messenger RNA of all higher eukaryotes. Although essential to cell viability and development, the exact role of m(6)A modification remains to be determined. The recent discovery of two m(6)A demethylases in mammalian cells highlighted the importance of m(6)A in basic biological functions and disease. Here we show that m(6)A is selectively recognized by the human YTH domain family 2 (YTHDF2) 'reader' protein to regulate mRNA degradation. We identified over 3,000 cellular RNA targets of YTHDF2, most of which are mRNAs, but which also include non-coding RNAs, with a conserved core motif of G(m(6)A)C. We further establish the role of YTHDF2 in RNA metabolism, showing that binding of YTHDF2 results in the localization of bound mRNA from the translatable pool to mRNA decay sites, such as processing bodies. The carboxy-terminal domain of YTHDF2 selectively binds to m(6)A-containing mRNA, whereas the amino-terminal domain is responsible for the localization of the YTHDF2-mRNA complex to cellular RNA decay sites. Our results indicate that the dynamic m(6)A modification is recognized by selectively binding proteins to affect the translation status and lifetime of mRNA.read more
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N6-methyladenosine Modulates Messenger RNA Translation Efficiency
Xiao Wang,Xiao Wang,Boxuan Simen Zhao,Boxuan Simen Zhao,Ian A Roundtree,Ian A Roundtree,Zhike Lu,Zhike Lu,Dali Han,Dali Han,Honghui Ma,Honghui Ma,Xiaocheng Weng,Xiaocheng Weng,Kai Chen,Kai Chen,Hailing Shi,Hailing Shi,Chuan He,Chuan He +19 more
TL;DR: In a unified mechanism of m(6)A-based regulation in the cytoplasm, YTHDF2-mediated degradation controls the lifetime of target transcripts, whereasYTHDF1-mediated translation promotion increases translation efficiency, ensuring effective protein production from dynamic transcripts that are marked by m( 6)A.
Journal ArticleDOI
A METTL3-METTL14 complex mediates mammalian nuclear RNA N6-adenosine methylation
Jianzhao Liu,Yanan Yue,Dali Han,Xiao Wang,Ye Fu,Liang Zhang,Guifang Jia,Miao Yu,Zhike Lu,Xin Deng,Qing Dai,Weizhong Chen,Chuan He +12 more
TL;DR: It is reported here that human METTL14 catalyzes m6A RNA methylation, and together with METTL3, the only previously known m 6A methyltransferase, these two proteins form a stable heterodimer core complex ofMETTL3-14 that functions in cellular m6 a deposition on mammalian nuclear RNAs.
Journal ArticleDOI
Dynamic RNA Modifications in Gene Expression Regulation
TL;DR: Roles for mRNA modification in nearly every aspect of the mRNA life cycle, as well as in various cellular, developmental, and disease processes are revealed.
Journal ArticleDOI
Mammalian WTAP is a regulatory subunit of the RNA N6-methyladenosine methyltransferase
Xiao-Li Ping,Bao-Fa Sun,Lu Wang,Wen Xiao,Xin Yang,Wenjia Wang,Samir Adhikari,Yue Shi,Ying Lv,Yu-Sheng Chen,Xu Zhao,Ang Li,Ying Yang,Ujwal Dahal,Xiao-Min Lou,Xi Liu,Jun Huang,Weiping Yuan,Xiaofan Zhu,Tao Cheng,Yong-Liang Zhao,Xinquan Wang,Jannie M. Rendtlew Danielsen,Feng Liu,Yun-Gui Yang +24 more
TL;DR: In this paper, two new components of the human m6A methyltransferase complex, Wilms' tumor 1-associating protein (WTAP) and methyl transferase like 14 (METTL14), were reported.
Journal ArticleDOI
Recognition of RNA N 6 -methyladenosine by IGF2BP proteins enhances mRNA stability and translation
Huilin Huang,Huilin Huang,Hengyou Weng,Hengyou Weng,Wen-Ju Sun,Xi Qin,Xi Qin,Hailing Shi,Hailing Shi,Huizhe Wu,Huizhe Wu,Huizhe Wu,Boxuan Simen Zhao,Boxuan Simen Zhao,Ana Mesquita,Chang Liu,Chang Liu,Celvie L. Yuan,Yueh-Chiang Hu,Stefan Hüttelmaier,Jennifer R. Skibbe,Rui Su,Rui Su,Xiaolan Deng,Xiaolan Deng,Xiaolan Deng,Lei Dong,Lei Dong,Miao Sun,Chenying Li,Chenying Li,Chenying Li,Sigrid Nachtergaele,Sigrid Nachtergaele,Yungui Wang,Yungui Wang,Chao Hu,Chao Hu,Kyle Ferchen,Kenneth D. Greis,Xi Jiang,Xi Jiang,Minjie Wei,Liang-Hu Qu,Jun-Lin Guan,Chuan He,Chuan He,Jian-Hua Yang,Jianjun Chen,Jianjun Chen +49 more
TL;DR: This work reports the insulin-like growth factor 2 mRNA-binding proteins as a distinct family of m6A readers that target thousands of mRNA transcripts through recognizing the consensus GG(m6A)C sequence, and identifies IGF2BPs as an additional class of N6-methyladenosine (m 6A) reader proteins.
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