Dynamic m6A modification and its emerging regulatory role in mRNA splicing

被引：38
作者：
Yang, Ying [1 ]
Sun, Bao-Fa [1 ]
Xiao, Wen [1 ,2 ]
Yang, Xin [1 ,2 ]
Sun, Hui-Ying [1 ,2 ,3 ]
Zhao, Yong-Liang [1 ]
Yang, Yun-Gui [1 ]
机构：
[1] Chinese Acad Sci, Beijing Inst Genom, Key Lab Genom & Precis Med, Beijing 100101, Peoples R China
[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China
[3] Sino Danish Ctr Sci & Educ, Beijing 100190, Peoples R China
来源：
SCIENCE BULLETIN | 2015年 / 60卷 / 01期
基金：
美国国家科学基金会;
关键词：
N-6-Methyl-adenosine (M(6)A); Methyltransferase; Demethylase; M(6)A binding protein; mRNA splicing; HETEROGENEOUS NUCLEAR-RNA; BINDING PROTEIN HUR; FTO GENE; WIDE ANALYSIS; N-6-METHYLADENOSINE RESIDUES; N-6-ADENOSINE METHYLATION; SEQUENCE SPECIFICITY; FACTOR YT521; SR PROTEINS; FAT MASS;
D O I：
10.1007/s11434-014-0695-6
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Recent studies on enzymes regulating dynamic N-6-methyl-adenosine (m(6)A) in RNA together with the findings from m(6)A-methylated RNA immunoprecipitation followed by high-throughput sequencing (MeRIP-seq/m(6) A-seq) have revealed a broad biological role of m(6)A in RNA processing, development, differentiation, metabolism and fertility. RNA m(6)A methylation is catalyzed by a multicomponent methyltransferase complex composed of at least three subunits: METTL3, METTL14 and Wilms tumor 1-associated protein (WTAP), in which METTL3 and METTL14 serve as catalytic subunits, while WTAP as regulatory subunit. Dioxygenases FTO and ALKBH5, as the first two known m(6)A demethylases, catalyze m(6)A removal. Five m(6)A-binding proteins are classified into cytoplasmic YT521-B homology (YTH) domain-containing family YTHDF1- 3 and nuclear YTHDC1-2. Perturbation of enzymatic activities catalyzing dynamic m(6)A results in altered expression of thousands of genes and affects mRNA stability and splicing at the cellular level. Here, we summarize recent discoveries about m(6)A methyltransferases (writers), demethylases (erasers) and binding proteins (readers), and further discuss the potential impacts of m(6)A on RNA processing, especially on mRNA splicing.
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收藏
页码：21 / 32
页数：12
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