Solution structure of the RNA recognition domain of METTL3-METTL14 N6-methyladenosine methyltransferase

• DOI: 10.1007/s13238-018-0518-7
• Publication Date: 2018-03-14T16:41:38Z
• Authors: Jinbo Huang; Xu Dong; Zhou Gong; Ling-Yun Qin; Shuai Yang; Yue-Ling Zhu; Xiang Wang; Delin Zhang; Tingting Zou; Ping Yin; Chun Tang
• Keywords: Linker; N6-Methyladenosine; Transferase

N 6 -methyladenosine (m A), a ubiquitous RNA modification, is installed by METTL3-METTL14 complex.The structure of the heterodimeric complex between methyltransferase domains (MTDs) METTL3 and METTL14 has been previously determined.However, MTDs alone possess no enzymatic activity.Here we present solution for zinc finger domain (ZFD) METTL3, inclusion which fulfills activity METTL3-METTL14.We show that ZFD specifically binds to an containing 5′-GGACU-3′ consensus sequence, but does not one without.The thus serves as target recognition domain, structural feature shown DNA methyltransferases, cooperates with catalysis.However, interaction specific extremely weak, binding affinity at several hundred micromolar under physiological conditions.The contains two CCCH-type fingers connected anti-parallel β-sheet.Mutational analysis NMR titrations have mapped functional interface contiguous surface.As division labor, RNA-binding comprises basic residues from 1 hydrophobic β-sheet 2. Further linker MTD flexible partially folded, may permit cooperation during catalysis.Together, characterization paves way elucidate atomic details entire process m A modification.