biostudies-literatureLi HNational Natural Science Foundation of Chinae108544https://www.ebi.ac.uk/biostudies/studies/S-EPMC8922252biostudies-literatureUnknown41(6)Since numerous RNAs and RBPs prevalently localize to active chromatin regions, many RNA-binding proteins (RBPs) may be potential transcriptional regulators. RBPs are generally thought to regulate transcription via noncoding RNAs. Here, we describe a distinct, dual mechanism of transcriptional regulation by the previously uncharacterized tRNA-modifying enzyme, hTrmt13. On one hand, hTrmt13 acts in the cytoplasm to catalyze 2'-O-methylation of tRNAs, thus regulating translation in a manner depending on its tRNA-modification activity. On the other hand, nucleus-localized hTrmt13 directly binds DNA as a transcriptional co-activator of key epithelial-mesenchymal transition factors, thereby promoting cell migration independent of tRNA-modification activity. These dual functions of hTrmt13 are muThe EMBO journalA dual role of human tRNA methyltransferase hTrmt13 in regulating translation and transcription.PMC89222523177084291940302319712303202204031870811Huang ZXLi HLi JZeng QYDong HXiong QPXu BYang WQLi CTWang EDLiu RJfalseA dual role of human tRNA methyltransferase hTrmt13 in regulating translation and transcription.Since numerous RNAs and RBPs prevalently localize to active chromatin regions, many RNA-binding proteins (RBPs) may be potential transcriptional regulators. RBPs are generally thought to regulate transcription via noncoding RNAs. Here, we describe a distinct, dual mechanism of transcriptional regulation by the previously uncharacterized tRNA-modifying enzyme, hTrmt13. On one hand, hTrmt13 acts in the cytoplasm to catalyze 2'-O-methylation of tRNAs, thus regulating translation in a manner depending on its tRNA-modification activity. On the other hand, nucleus-localized hTrmt13 directly binds DNA as a transcriptional co-activator of key epithelial-mesenchymal transition factors, thereby promoting cell migration independent of tRNA-modification activity. These dual functions of hTrmt13 are mu2022-01-01T00:00:00Z2022 Mar2025-04-25T23:00:58.988Z2025-02-19T03:58:58.552ZS-EPMC89222523485040910.15252/embj.2021108544