Nature：N6-甲基腺苷广泛修饰的mRNA被蛋白YTHDF2识别

芝加哥大学化学与生物物理动力学研究所的研究人员发现，在人类细胞中，蛋白YTHDF2能够识别被N6-甲基腺苷广泛修饰的mRNA，不仅是mRNA，而且还在各种非编码rna中。相关文章发表于2013年11月27日的《Nature》杂志上。

Nature：N6-甲基腺苷广泛修饰的mRNA被蛋白YTHDF2识别

高等真核生物的信使rna (mRNA)被N6-甲基腺苷广泛修饰，但这种修饰的功能作用一直不清楚。

现在，Chuan He及同事发现，在人类细胞中，这些被修饰的碱基是被一组名为YTHDF2的蛋白识别的，不仅是在mRNA中，而且还在各种非编码RNA中。

一旦结合，这些蛋白便通过将RNA定向到细胞RNA降解点上来介导它的降解。该修饰过程以这种方式充当RNA寿命的一个调控因子。

原文摘要：

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

N6-methyladenosine (m6A) 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 m6A modification remains to be determined. The recent discovery of two m6A demethylases in mammalian cells highlighted the importance of m6A in basic BioLogical functions and disease. Here we show that m6A 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(m6A)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 m6A-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 m6A modification is recognized by selectively binding proteins to affect the translation status and lifetime of mRNA.