Solution structure of the RNA recognition domain of METTL3-METTL14 N(6)-methyladenosine methyltransferase.
Solution structure of the RNA recognition domain of METTL3-METTL14 N(6)-methyladenosine methyltransferase.
复制标题
METTL3-METTL14 N-6-甲基腺苷甲基转移酶RNA识别域的溶液结构
DOI：
10.1007/s13238-018-0518-7
复制
发表时间：
2019-04
期刊：
影响因子：
21.1
通讯作者：
Tang C
中科院分区：
文献类型：
--
作者：
Huang J;Dong X;Gong Z;Qin LY;Yang S;Zhu YL;Wang X;Zhang D;Zou T;Yin P;Tang C
N6-methyladenosine (m6A), a ubiquitous RNA modification, is installed by METTL3-METTL14 complex. The structure of the heterodimeric complex between the methyltransferase domains (MTDs) of METTL3 and METTL14 has been previously determined. However, the MTDs alone possess no enzymatic activity. Here we present the solution structure for the zinc finger domain (ZFD) of METTL3, the inclusion of which fulfills the methyltransferase activity of METTL3-METTL14. We show that the ZFD specifically binds to an RNA containing 5′-GGACU-3′ consensus sequence, but does not to one without. The ZFD thus serves as the target recognition domain, a structural feature previously shown for DNA methyltransferases, and cooperates with the MTDs of METTL3-METTL14 for catalysis. However, the interaction between the ZFD and the specific RNA is extremely weak, with the binding affinity at several hundred micromolar under physiological conditions. The ZFD contains two CCCH-type zinc fingers connected by an anti-parallel β-sheet. Mutational analysis and NMR titrations have mapped the functional interface to a contiguous surface. As a division of labor, the RNA-binding interface comprises basic residues from zinc finger 1 and hydrophobic residues from β-sheet and zinc finger 2. Further we show that the linker between the ZFD and MTD of METTL3 is flexible but partially folded, which may permit the cooperation between the two domains during catalysis. Together, the structural characterization of METTL3 ZFD paves the way to elucidate the atomic details of the entire process of RNA m6A modification. The online version of this article (10.1007/s13238-018-0518-7) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
16.6
作者：
Liu, Zhu;Zhang, Wei-Ping;Xing, Qiong;Ren, Xuefeng;Liu, Maili;Tang, Chun
通讯作者：
Tang, Chun
影响因子：
64.8
作者：
Lence, Tina;Akhtar, Junaid;Roignant, Jean-Yves
通讯作者：
Roignant, Jean-Yves
影响因子：
2.9
作者：
Park S;Phukan PD;Zeeb M;Martinez-Yamout MA;Dyson HJ;Wright PE
通讯作者：
Wright PE
影响因子：
2.7
作者：
Freiburger, Lee;Sonntag, Miriam;Sattler, Michael
通讯作者：
Sattler, Michael
影响因子：
16.8
作者：
Murn J;Teplova M;Zarnack K;Shi Y;Patel DJ
通讯作者：
Patel DJ