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. © 2021 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

Citation

Hao Li, Han Dong, Beisi Xu, Qing-Ping Xiong, Cai-Tao Li, Wen-Qing Yang, Jing Li, Zhi-Xuan Huang, Qi-Yu Zeng, En-Duo Wang, Ru-Juan Liu. A dual role of human tRNA methyltransferase hTrmt13 in regulating translation and transcription. The EMBO journal. 2022 Mar 15;41(6):e108544

Mesh Tags

Substances

PMID: 34850409

search → result