APM OpenIR
Solution structure of the RNA recognition domain of METTL3-METTL14 N-6-methyladenosine methyltransferase
Huang, Jinbo1,2; Dong, Xu3,4; Gong, Zhou3,4; Qin, Ling-Yun3,4; Yang, Shuai3,4; Zhu, Yue-Ling3,4; Wang, Xiang1,2; Zhang, Delin1,2; Zou, Tingting1,2; Yin, Ping1,2; Tang, Chun3,4
2019-04-01
Source PublicationPROTEIN & CELL
ISSN1674-800X
Volume10Issue:4Pages:272-284
AbstractN-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.
KeywordRNA modification N-6-methyladenosine METTL3 target recognition domain zinc finger paramagnetic relaxation enhancement
Funding OrganizationNational 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
DOI10.1007/s13238-018-0518-7
WOS KeywordMESSENGER-RNA ; NUCLEAR-RNA ; PROTEIN ; METHYLATION ; N6-METHYLADENOSINE ; REVEALS
Language英语
Funding ProjectNational 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]
Funding OrganizationNational 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
WOS Research AreaCell Biology
WOS SubjectCell Biology
WOS IDWOS:000461295400004
PublisherSPRINGEROPEN
Citation statistics
Cited Times:16[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.apm.ac.cn/handle/112942/13927
Collection中国科学院武汉物理与数学研究所
Corresponding AuthorYin, Ping; Tang, Chun
Affiliation1.Huazhong Agr Univ, Natl Key Lab Crop Genet Improvement, Wuhan 430070, Peoples R China
2.Huazhong Agr Univ, Natl Ctr Plant Gene Res, Wuhan 430070, Peoples R China
3.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
4.Chinese Acad Sci, Natl Ctr Magnet Resonance Wuhan, Wuhan Inst Phys & Math, Wuhan 430071, Peoples R China
Recommended Citation
GB/T 7714
Huang, Jinbo,Dong, Xu,Gong, Zhou,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 Huang, Jinbo.,Dong, Xu.,Gong, Zhou.,Qin, Ling-Yun.,Yang, Shuai.,...&Tang, Chun.(2019).Solution structure of the RNA recognition domain of METTL3-METTL14 N-6-methyladenosine methyltransferase.PROTEIN & CELL,10(4),272-284.
MLA Huang, Jinbo,et al."Solution structure of the RNA recognition domain of METTL3-METTL14 N-6-methyladenosine methyltransferase".PROTEIN & CELL 10.4(2019):272-284.
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