More than 90 different modified nucleosides have been identified in tRNA. Among the tRNA modifications, the 7-methylguanosine (m
7G) modification is found widely in eubacteria, eukaryotes, and a few archaea. In most cases, the m
7G modification occurs at position 46 in the variable region and is a product of tRNA (m
7G46) methyltransferase. The m
7G46 modification forms a tertiary base pair with C13-G22, and stabilizes the tRNA structure. A reaction mechanism for eubacterial tRNA m
7G methyltransferase has been proposed based on the results of biochemical, bioinformatic, and structural studies. However, an experimentally determined mechanism of methyl-transfer remains to be ascertained. The physiological functions of m
7G46 in tRNA have started to be determined over the past decade. For example, tRNA m
7G46 or tRNA (m
7G46) methyltransferase controls the amount of other tRNA modifications in thermophilic bacteria, contributes to the pathogenic infectivity, and is also associated with several diseases. In this review, information of tRNA m
7G modifications and tRNA m
7G methyltransferases is summarized and the differences in reaction mechanism between tRNA m
7G methyltransferase and rRNA or mRNA m
7G methylation enzyme are discussed.
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