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Página principal > Artículos > Artículos publicados > Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer |
Fecha: | 2020 |
Resumen: | 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 RNAs (mRNAs). 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. |
Ayudas: | Instituto de Salud Carlos III IFI17-00006 Ministerio de Ciencia e Innovación RTI2018-094049-B-I00 Ministerio de Ciencia e Innovación SAF2014-55000 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017SGR1080 |
Nota: | Altres ajuts: Funding for this research was provided by the Asociación Española Contra el Cáncer Scientific Foundation (Accelerator Award A26825); and the Olga Torres Foundation. |
Derechos: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. |
Lengua: | Anglès |
Documento: | Article ; recerca ; Versió publicada |
Materia: | Cancer ; Epigenetics ; Transfer RNA |
Publicado en: | Proceedings of the National Academy of Sciences of the United States of America, Vol. 117 Núm. 34 (25 2020) , p. 20785-20793, ISSN 1091-6490 |
9 p, 2.0 MB |