The team of Ma Jinbiao, Wang Hailin, Dong Aiwu and Shi Yang worked together to reveal the structure and function of Arabidopsis METTL4

The team of Ma Jinbiao, Wang Hailin, Dong Aiwu and Shi Yang worked together to reveal the structure and function of Arabidopsis METTL4

On September 26, 2022, the team of Professor Ma Jinbiao and Professor Dong Aiwu of the School of Life Sciences and the State Key Laboratory of Genetic Engineering of Fudan University, the team of researchers Wang Hailin of the Research Center for Ecology and Environment of the Chinese Academy of Sciences, and the team of Professor Shi Yang of the Ludwig Cancer Institute of the University of Oxford, published an online article entitled "Structural insights into molecular mechanism" in the journal Nature Communications for N 6-adenosine methylation by MT-A70 family methyltransferase METTL4" paper.

Enzymatic RNA covalent modification is an important epigenetic mechanism that fine-modulates a variety of cellular activities
in eukaryotes.

METTL4 is widespread in eukaryotes and belongs to the MT-A70 family along with the traditional RNA^m6Amethyltransferase METTL3 and METTL14, and has a conserved MTA domain
.

Figure 1.
Arabidopsis thaliana METTL4 leads to the catalytic activity (d-g) of N6-adenosine methylation of early flowering (a-b)
and its specific modification U2 snRNA 31st position Am.

Subsequently, the team analyzed a series of crystal structures such as METTL4 itself and its binding cofactors SAM/SAH/FG, especially the crystal structure of the ternary complex of METTL4 binding SAH and its catalytic pocket binding Am substrate obtained by immersion, revealing the molecular mechanism of METTL4 specific recognition of Am (Figure 2d-e).

Figure 2 Catalytic mechanism of Arabidopsis thaliana METTL4 binding SAH and Am substrate ternary complex crystal structure (a-c) and its specificity to recognize Am (d-f) and methylation modified N6-adenosine (g-i
).

Luo Qiang, a doctoral student jointly trained by Professor Ma Jinbiao and Professor Dong Aiwu, Mo Jiezhen, a doctoral student in Wang Hailin's Laboratory, and Professor Chen Hao of Southern University of Science and Technology are co-first authors
.

Paper link: https://doi.