Journal ArticleDOI
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
TLDR
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.Abstract:
An extensive repertoire of modifications is known to underlie the versatile coding, structural and catalytic functions of RNA, but it remains largely uncharted territory. Although biochemical studies indicate that N(6)-methyladenosine (m(6)A) is the most prevalent internal modification in messenger RNA, an in-depth study of its distribution and functions has been impeded by a lack of robust analytical methods. Here we present the human and mouse m(6)A modification landscape in a transcriptome-wide manner, using a novel approach, m(6)A-seq, based on antibody-mediated capture and massively parallel sequencing. We identify over 12,000 m(6)A sites characterized by a typical consensus in the transcripts of more than 7,000 human genes. Sites preferentially appear in two distinct landmarks--around stop codons and within long internal exons--and are highly conserved between human and mouse. Although most sites are well preserved across normal and cancerous tissues and in response to various stimuli, a subset of stimulus-dependent, dynamically modulated sites is identified. Silencing the m(6)A methyltransferase significantly affects gene expression and alternative splicing patterns, resulting in modulation of the p53 (also known as TP53) signalling pathway and apoptosis. Our findings therefore suggest that RNA decoration by m(6)A has a fundamental role in regulation of gene expression.read more
Citations
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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
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.
Journal ArticleDOI
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.
References
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Book
ggplot2: Elegant Graphics for Data Analysis
TL;DR: This book describes ggplot2, a new data visualization package for R that uses the insights from Leland Wilkisons Grammar of Graphics to create a powerful and flexible system for creating data graphics.
Journal ArticleDOI
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome
TL;DR: Bowtie extends previous Burrows-Wheeler techniques with a novel quality-aware backtracking algorithm that permits mismatches and can be used simultaneously to achieve even greater alignment speeds.
Journal ArticleDOI
BEDTools: a flexible suite of utilities for comparing genomic features
Aaron R. Quinlan,Ira M. Hall +1 more
TL;DR: A new software suite for the comparison, manipulation and annotation of genomic features in Browser Extensible Data (BED) and General Feature Format (GFF) format, which allows the user to compare large datasets (e.g. next-generation sequencing data) with both public and custom genome annotation tracks.
Journal ArticleDOI
Differential expression analysis for sequence count data.
Simon Anders,Wolfgang Huber +1 more
TL;DR: A method based on the negative binomial distribution, with variance and mean linked by local regression, is proposed and an implementation, DESeq, as an R/Bioconductor package is presented.
Journal ArticleDOI
Model-based Analysis of ChIP-Seq (MACS)
Yong Zhang,Tao Liu,Clifford A. Meyer,Jérôme Eeckhoute,David S. Johnson,Bradley E. Bernstein,Bradley E. Bernstein,Chad Nusbaum,Richard M. Myers,Myles Brown,Wei Li,X. Shirley Liu +11 more
TL;DR: This work presents Model-based Analysis of ChIP-Seq data, MACS, which analyzes data generated by short read sequencers such as Solexa's Genome Analyzer, and uses a dynamic Poisson distribution to effectively capture local biases in the genome, allowing for more robust predictions.
Related Papers (5)
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