The dynamic N(1)-methyladenosine methylome in eukaryotic messenger RNA.
The dynamic N(1)-methyladenosine methylome in eukaryotic messenger RNA.
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DOI：
10.1038/nature16998
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发表时间：
2016-02-25
期刊：
影响因子：
64.8
通讯作者：
He C
中科院分区：
文献类型：
--
作者：
Dominissini D;Nachtergaele S;Moshitch-Moshkovitz S;Peer E;Kol N;Ben-Haim MS;Dai Q;Di Segni A;Salmon-Divon M;Clark WC;Zheng G;Pan T;Solomon O;Eyal E;Hershkovitz V;Han D;Doré LC;Amariglio N;Rechavi G;He C
基因表达可以通过动态和可逆的RNA修饰进行转录后调控。最近一个值得注意的例子是N6-甲基腺苷（m6 A），它影响信使RNA（mRNA）的定位，稳定性，翻译和剪接。在这里，我们报告了一种新的mRNA修饰，N1-甲基腺苷（m1A），发生在真核细胞中的数千种不同的基因转录本上，从酵母到哺乳动物，在人类中估计平均转录化学计量为20%。采用新开发的测序方法，我们表明，m1A是丰富的第一个剪接位点上游的起始密码子周围：它优先装饰更多的结构化区域周围的典型和替代翻译起始位点，是动态的生理条件下，并与蛋白质的生产呈正相关。这些独特的特征在小鼠和人类细胞中高度保守，强烈表明m1A在促进甲基化mRNA翻译中的功能作用。
Gene expression can be regulated post-transcriptionally through dynamic and reversible RNA modifications. A recent noteworthy example is N6-methyladenosine (m6A), which affects messenger RNA (mRNA) localization, stability, translation and splicing. Here we report on a new mRNA modification, N1-methyladenosine (m1A), that occurs on thousands of different gene transcripts in eukaryotic cells, from yeast to mammals, at an estimated average transcript stoichiometry of 20% in humans. Employing newly developed sequencing approaches, we show that m1A is enriched around the start codon upstream of the first splice site: it preferentially decorates more structured regions around canonical and alternative translation initiation sites, is dynamic in response to physiological conditions, and correlates positively with protein production. These unique features are highly conserved in mouse and human cells, strongly indicating a functional role for m1A in promoting translation of methylated mRNA.