Solution structure of the RNA recognition domain of METTL3-METTL14 N-6-methyladenosine methyltransferase

doi:10.1007/s13238-018-0518-7

	Solution structure of the RNA recognition domain of METTL3-METTL14 N-6-methyladenosine methyltransferase
	Tang, Chun 1,2; Yin, Ping 3,4; Zou, Tingting 3,4; Zhang, Delin 3,4; Wang, Xiang 3,4; Zhu, Yue-Ling 1,2; Yang, Shuai 1,2; Qin, Ling-Yun 1,2; Gong, Zhou 1,2; Dong, Xu 1,2
刊名	PROTEIN & CELL
	2019-04-01
卷号	10 期号:4 页码:272-284
关键词	RNA modification N-6-methyladenosine METTL3 target recognition domain zinc finger paramagnetic relaxation enhancement
ISSN号	1674-800X
DOI	10.1007/s13238-018-0518-7
英文摘要	N-6-methyladenosine (m(6)A), 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 -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 -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 m(6)A modification.
资助项目	National Key R&D Program of China[2016YFA0501200] ; Chinese Ministry of Science and Technology[2015CB910900] ; National Natural Science Foundation of China[91753132] ; National Natural Science Foundation of China[31770799] ; National Natural Science Foundation of China[31722017] ; National Natural Science Foundation of China[31400735] ; National Natural Science Foundation of China[31400644] ; Fok Ying-Tong Education Foundation[151021] ; Fundamental Research Funds for the Central Universities[2017PY031]
WOS关键词	MESSENGER-RNA ; NUCLEAR-RNA ; PROTEIN ; METHYLATION ; N6-METHYLADENOSINE ; REVEALS
WOS研究方向	Cell Biology
语种	英语
出版者	SPRINGEROPEN
WOS记录号	WOS:000461295400004
资助机构	National Key R&D Program of China ; National Key R&D Program of China ; Chinese Ministry of Science and Technology ; Chinese Ministry of Science and Technology ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Fok Ying-Tong Education Foundation ; Fok Ying-Tong Education Foundation ; Fundamental Research Funds for the Central Universities ; Fundamental Research Funds for the Central Universities ; National Key R&D Program of China ; National Key R&D Program of China ; Chinese Ministry of Science and Technology ; Chinese Ministry of Science and Technology ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Fok Ying-Tong Education Foundation ; Fok Ying-Tong Education Foundation ; Fundamental Research Funds for the Central Universities ; Fundamental Research Funds for the Central Universities ; National Key R&D Program of China ; National Key R&D Program of China ; Chinese Ministry of Science and Technology ; Chinese Ministry of Science and Technology ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Fok Ying-Tong Education Foundation ; Fok Ying-Tong Education Foundation ; Fundamental Research Funds for the Central Universities ; Fundamental Research Funds for the Central Universities ; National Key R&D Program of China ; National Key R&D Program of China ; Chinese Ministry of Science and Technology ; Chinese Ministry of Science and Technology ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; Fok Ying-Tong Education Foundation ; Fok Ying-Tong Education Foundation ; Fundamental Research Funds for the Central Universities ; Fundamental Research Funds for the Central Universities
内容类型	期刊论文
源URL	[http://ir.wipm.ac.cn/handle/112942/13926]
专题	中国科学院武汉物理与数学研究所
通讯作者	Tang, Chun; Yin, Ping
作者单位	1.Chinese Acad Sci, Natl Ctr Magnet Resonance Wuhan, Wuhan Inst Phys & Math, Wuhan 430071, Peoples R China 2.Chinese Acad Sci, CAS Key Lab Magnet Resonance Biol Syst, State Key Lab Magnet Resonance & Atom Mol Phys, Wuhan Inst Phys & Math, Wuhan 430071, Peoples R China 3.Huazhong Agr Univ, Natl Ctr Plant Gene Res, Wuhan 430070, Peoples R China 4.Huazhong Agr Univ, Natl Key Lab Crop Genet Improvement, Wuhan 430070, Peoples R China
推荐引用方式 GB/T 7714	Tang, Chun,Yin, Ping,Zou, Tingting,et al. Solution structure of the RNA recognition domain of METTL3-METTL14 N-6-methyladenosine methyltransferase[J]. PROTEIN & CELL,2019,10(4):272-284.
APA	Tang, Chun.,Yin, Ping.,Zou, Tingting.,Zhang, Delin.,Wang, Xiang.,...&Huang, Jinbo.(2019).Solution structure of the RNA recognition domain of METTL3-METTL14 N-6-methyladenosine methyltransferase.PROTEIN & CELL,10(4),272-284.
MLA	Tang, Chun,et al."Solution structure of the RNA recognition domain of METTL3-METTL14 N-6-methyladenosine methyltransferase".PROTEIN & CELL 10.4(2019):272-284.