A dual role of human tRNA methyltransferase hTrmt13 in regulating translation and transcription. (1st December 2021)

• Record Type: Journal Article
• Authors: Li, Hao; Dong, Han; Xu, Beisi; Xiong, Qing‐Ping; Li, Cai‐Tao; Yang, Wen‐Qing; Li, Jing; Huang, Zhi‐Xuan; Zeng, Qi‐Yu; Wang, En‐Duo; Liu, Ru‐Juan
• Is Part Of: EMBO journal. Volume 41:Number 6(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-12-01
• Subjects: cancer metastasis -- RNA modification -- transcription -- translation -- tRNA; Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.2021108544
• Languages: English
• ISSNs: 0261-4189

Abstract

Abstract: 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. Synopsis: tRNA methyltransferases regulate translation through tRNA modification, while chromatin‐associated RBPs are thought to regulate transcription primarily though lncRNAs. Here, human tRNA methyltransferase hTrmt13 is found to have an unexpected additional nuclear function in regulating transcription. Cytoplasmic hTrmt13 regulates protein translation dependent on its tRNA 2'‐ O ‐methylation activity. Nuclear hTrmt13 directly binds DNA to promote transcription, independent of its catalytic activity. Nuclear hTrmt13 promotes cell migration and cancer metastasis by acting as a transcriptional co‐activator. Abstract : hTrmt13 regulates gene expression via translation in the cytoplasm, but also by acting in a non‐catalytic manner as a transcriptional coactivator.