m6A in mRNA coding regions promotes translation via the RNA helicase-containing YTHDC2

被引：313
作者：
Mao, Yuanhui [1 ]
Dong, Leiming [1 ]
Liu, Xiao-Min [1 ]
Guo, Jiayin [2 ]
Ma, Honghui [3 ]
Shen, Bin [2 ]
Qian, Shu-Bing [1 ]
机构：
[1] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA
[2] Nanjing Med Univ, Dept Histol & Embryol, State Key Lab Reprod Med, Nanjing 211166, Jiangsu, Peoples R China
[3] Tongji Univ, East Hosp, Key Lab Arrhythmias, Minist Educ China,Sch Med, Shanghai 200120, Peoples R China
来源：
NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期
基金：
美国国家卫生研究院;
关键词：
SINGLE-NUCLEOTIDE-RESOLUTION; NUCLEAR-RNA; N-6-METHYLADENOSINE; METHYLATION; REVEALS; PROTEIN; DINUCLEOTIDE; M6A;
D O I：
10.1038/s41467-019-13317-9
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：
Dynamic mRNA modification in the form of N-6-methyladenosine (m(6)A) adds considerable richness and sophistication to gene regulation. The m(6)A mark is asymmetrically distributed along mature mRNAs, with approximately 35% of m(6)A residues located within the coding region (CDS). It has been suggested that methylation in CDS slows down translation elongation. However, neither the decoding feature of endogenous mRNAs nor the physiological significance of CDS m(6)A has been clearly defined. Here, we found that CDS m(6)A leads to ribosome pausing in a codon-specific manner. Unexpectedly, removing CDS m(6)A from these transcripts results in a further decrease of translation. A systemic analysis of RNA structural datasets revealed that CDS m(6)A positively regulates translation by resolving mRNA secondary structures. We further demonstrate that the elongation-promoting effect of CDS methylation requires the RNA helicase-containing m(6)A reader YTHDC2. Our findings established the physiological significance of CDS methylation and uncovered non-overlapping function of m(6)A reader proteins.
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页数：11
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