A 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 mutually exclusive, as it can bind either DNA or tRNA through its CHHC zinc finger domain. Finally, we find that hTrmt13 expression is tightly associated with poor prognosis and survival in diverse cancer patients. Our discovery of the noncatalytic roles of an RNA-modifying enzyme provides a new perspective for understanding epitranscriptomic regulation.

Automated summary

The previously uncharacterized tRNA-modifying enzyme hTrmt13 is found to regulate transcription in a dual mechanism, catalyzing tRNA 2'-O-methylation in the cytoplasm for translation regulation and binding DNA as a transcriptional co-activator in the nucleus for promoting cell migration. These dual functions are mutually exclusive and the expression of hTrmt13 is correlated with poor prognosis in cancer patients. This discovery provides a new perspective for epitranscriptomic regulation.