Yu Jianxiu revealed the molecular mechanism of protein modification to regulate the catalytic function of the key enzyme METTL3 modified by RNA-m6A for the first time

YuJianxiu from Shanghai Jiao Tong University School of Medicine, department of biochemistry and molecular biology published in the international famous academic journal Nucleic Acids Research (impact factor 10.162) an article titled “SUMOylation of m6A - RNA methyltransferase METTL3 modulates its function”.This study is the first to reveal a new molecular mechanism for SUMO modification to regulate the catalytic function of METTL3, a key enzyme of m6A modification.

In the last two to three years, the modification of RNA n6-methyladenine (m6A) has become one of the hottest and most advanced research directions.M6A modification is the most common and abundant modification of eukaryotic RNA.METTL3 is one of the most important constituent proteins in m6A methyltransferase complex. It is mainly responsible for catalyzing the m6A modification of RNA molecules on n6-methyladenine.The loss or abnormal expression of METTL3 will affect the m6A level of intracellular RNA, and further affect the degradation and translation of mRNA and the generation of microRNA, which may lead to the occurrence of human diseases.At present, most research focused on the METTL3 generate the role and m6A in m6A abnormal level in such aspects as its role in the development of human diseases, but in regulating METTL3 itself and the regulation on the methylation transferase function will produce what kind of influence, etc., there is almost no research team involved.Yu Jianxiu‘s team have long been good at studying tumor protein modification (PTM) and RNA, identified the SUMO modification and function of METTL3.They found that the cells on the low type specific protease Senp1 can obviously reduce the intracellular RNA m6A modification level, further find METTL3 in its 177th / 215/211/212 lysine residues on the SUMO modification.This modification did not affect the stability of the protein and its localization in cells, nor did it alter the interaction between the protein and METTL14 and WTAP.Through cell lines and in vitro experiments, they found that SUMO modification of METTL3 significantly inhibited the activity of m6A methylated transferase, promoted the formation of specific cancer cells and tumor formation.This study elucidated the molecular mechanism of SUMO modification of METTL3 to regulate the catalytic function of m6A modification.This study is the first to introduce PTM into the domain of m6A modification, namely the first protein modification of m6A modification catalytic complex.The team believes that these key proteins and their compounds must also have other PTMs, such as ubiquitination and acetylation, to be discovered.In the paper review, I received high recognition from the paper review experts.This paper answers a scientific question about how METTL3 regulates itself (METTL3 SUMOylation and m6A modification regulation, an empty question of METTL3 self-regulation).Interestingly, another referee specifically mentionedthat Yu jianxiu’s lab has made significant contributions to the SUMO field.