TRMT2A is a novel cell cycle regulator that suppresses cell proliferation

During the maturation of transfer RNA (tRNA), a variety of chemical modifications can be introduced at specific nucleotide positions post-transcriptionally. 5-Methyluridine (m⁵U) is one of the most common and conserved modifications from eubacteria to eukaryotes. Although TrmA protein in Escherichia coli and Trm2p protein in Saccharomyces cerevisiae, which are responsible for the 5-methylation of uracil at position 54 (m⁵U54) on tRNA, are well characterized, the biological function of the U54 methylation responsible enzyme in mammalian species remains largely unexplored. Here, we show that the mammalian tRNA methyltransferase 2 homolog A (TRMT2A) protein harbors an RNA recognition motif in the N-terminus and the conserved uracil-C5-methyltransferase domain of the TrmA family in the C-terminus. TRMT2A predominantly localizes to the nucleus in HeLa cells. TRMT2A-overexpressing cells display decreased cell proliferation and altered DNA content, while TRMT2A-deficient cells exhibit increased growth. Thus, our results reveal the inhibitory role of TRMT2A on cell proliferation and cell cycle control, providing evidence that TRMT2A is a candidate cell cycle regulator in mammals.