Human cytoplasmic tRNA3-methylcytosine modified enzyme substrate mutual exclusive recognition model

Among all RNA molecules in a cell, tRNA contains the most dense and diverse post-transcriptional repairs

In this study, the researchers obtained high-purity METTTL2A, METTTL2B and METTTL6, and successfully recombined the m ³ C32 modification activity of METT2A on tRNAThr for the first time; with the help of seryl -tRNA synthetase (SerRS), they successfully recombined METTL6 Modification activity for m ³ C32 of tRNA ^Ser (GCU) ; it is found that both METL2A and METTTL2B are expressed in vivo, while the in vitro modification activity of METTTL2B is only one-tenth of that of METTTL2A; further in vitro biochemical analysis found that G35 and 37th t ⁶ A modification (t ⁶ A37) is a necessary but insufficient condition for tRNA ^{Thr to} form m ³ C32 modification, and the anticodon loop and long variable loop of tRNA ^Ser (GCU) are both key factors in the occurrence of m ³ C32 modification.

This study successfully recombined the methylation modification activity of human cytoplasmic tRNA m ³ C32 methyltransferases METL2A and METL6 for the first time ; explained the molecular mechanism of tRNA ^Thr and tRNA ^Ser (GCU) m ³ C32 modification; clarified the substrates of METL2A and METL6 Selective mechanism, proposed a model of selective mutual exclusive recognition of substrates

Xueling Mao, a doctoral student at the Center for Excellence in Molecular and Cellular Sciences, is the first author of this article, and researcher Zhou Xiaolong is the corresponding author of this article

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The mutual exclusive recognition model of METTL2A and METTL6 substrates