N6-methyladenosine-dependent regulation of messenger RNA stability.
N6-methyladenosine-dependent regulation of messenger RNA stability.
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作者：
N6-甲基腺苷（m6 A）是所有高等真核生物信使RNA（mRNA）中最普遍的内部（非帽）修饰。虽然对细胞活力和发育至关重要，但m6 A修饰的确切作用仍有待确定。最近在哺乳动物细胞中发现的两种m6 A脱甲基酶突出了m6 A在基本生物学功能和疾病中的重要性。在这里，我们表明m6 A被人YTH结构域家族2（YTHDF 2）蛋白选择性识别以调节mRNA降解。我们鉴定了YTHDF 2的3,000多种细胞RNA靶标，其中大部分是mRNA，但也包括非编码RNA，具有保守的核心基序G（m6 A）C。我们进一步确定了YTHDF 2在RNA代谢中的作用，表明YTHDF 2的结合导致结合mRNA从可翻译库定位到mRNA衰变位点，如加工体。YTHDF 2的C-末端结构域选择性地结合到含有m6 A的mRNA，而N-末端结构域负责YTHDF 2-mRNA复合物定位到细胞RNA衰变位点。我们的研究结果表明，动态m6 A修饰被选择性结合蛋白识别，影响mRNA的翻译状态和寿命。
N6-methyladenosine (m6A) is the most prevalent internal (non-cap) modification present in the messenger RNA (mRNA) 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) 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 C-terminal domain of YTHDF2 selectively binds to m6A-containing mRNA whereas the N-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 selective-binding proteins to affect the translation status and lifetime of mRNA.
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影响因子：
64.5
作者：
Hafner M;Landthaler M;Burger L;Khorshid M;Hausser J;Berninger P;Rothballer A;Ascano M Jr;Jungkamp AC;Munschauer M;Ulrich A;Wardle GS;Dewell S;Zavolan M;Tuschl T
通讯作者：
Tuschl T
影响因子：
16
作者：
Mukherjee N;Corcoran DL;Nusbaum JD;Reid DW;Georgiev S;Hafner M;Ascano M Jr;Tuschl T;Ohler U;Keene JD
通讯作者：
Keene JD
影响因子：
14.9
作者：
Clancy, MJ;Shambaugh, ME;Bokar, JA
通讯作者：
Bokar, JA
DOI：
10.3791/2034
发表时间：
2010-07-02
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Hafner, Markus;Landthaler, Markus;Tuschl, Thomas
通讯作者：
Tuschl, Thomas
影响因子：
64.5
作者：
Meyer KD;Saletore Y;Zumbo P;Elemento O;Mason CE;Jaffrey SR
通讯作者：
Jaffrey SR