Rosselló Tortella, MargalidaLlinàs Arias, PereSakaguchi, YurikoMiyauchi, KenjyoDavalos, VeronicaSetién, FernandoCalleja Cervantes, Maria E.Pineyro, DavidMartínez Gomez, JesúsGuil, SoniaJoshi, RickyVillanueva Garatachea, AlbertoSuzuki, TsutomuEsteller, Manel2021-01-282021-01-282020-08-25https://hdl.handle.net/2445/173469Transfer 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.9 p.application/pdfengcc by (c) Rosselló Tortella et al., 2020http://creativecommons.org/licenses/by/3.0/es/Càncer colorectalEpigenèticaColorectal cancerEpigeneticsinfo:eu-repo/semantics/article7030312021-01-25info:eu-repo/semantics/openAccess32778592