期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 117, 期 34, 页码 20785-20793出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2003358117
关键词
epigenetics; transfer RNA; cancer
资金
- Secretariat for Universities and Research of the Ministry of Business and Knowledge of the Government of Catalonia [2017SGR1080]
- Ministerio de Ciencia, Innovacion y Universidades, Agencia Estatal de Investigacion, Fondo Europeo de Desarrollo Regional [RTI2018-094049-B-I00, SAF2014-55000]
- Asociacion Espanola Contra el Cancer Scientific Foundation [A26825]
- Olga Torres Foundation
- Instituto de Salud Carlos III (contratos Predoctorales de Formacion en Investigacion y Salud) [IFI17/00006]
Transfer RNA (tRNA) activity is tightly regulated to provide a physiological protein translation, and tRNA chemical modifications control its function in a complex with ribosomes and messenger RNA5 (mRNA5). In this regard, the correct hypermodification of position G37 of phenylalanine-tRNA, adjacent to the anticodon, is critical to prevent ribosome frameshifting events. Here we report that the tRNA-yW Synthesizing Protein 2 (TYW2) undergoes promoter hypermethylation-associated transcriptional silencing in human cancer, particularly in colorectal tumors. The epigenetic loss of TYW2 induces guanosine hypomodification in phenylalanine-tRNA, an increase in -1 ribosome frameshift events, and down-regulation of transcripts by mRNA decay, such as of the key cancer gene ROBO1. Importantly, TYW2 epigenetic inactivation is linked to poor overall survival in patients with early-stage colorectal cancer, a finding that could be related to the observed acquisition of enhanced migration properties and epithelial-to-mesenchymal features in the colon cancer cells that harbor TYW2 DNA methylation-associated loss. These findings provide an illustrative example of how epigenetic changes can modify the epitranscriptome and further support a role for tRNA modifications in cancer biology.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据