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http://hdl.handle.net/2445/173469
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DC Field | Value | Language |
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dc.contributor.author | Rosselló Tortella, Margalida | - |
dc.contributor.author | Llinàs Arias, Pere | - |
dc.contributor.author | Sakaguchi, Yuriko | - |
dc.contributor.author | Miyauchi, Kenjyo | - |
dc.contributor.author | Davalos, Veronica | - |
dc.contributor.author | Setién, Fernando | - |
dc.contributor.author | Calleja Cervantes, Maria E. | - |
dc.contributor.author | Pineyro, David | - |
dc.contributor.author | Martínez Gomez, Jesús | - |
dc.contributor.author | Guil, Sonia | - |
dc.contributor.author | Joshi, Ricky | - |
dc.contributor.author | Villanueva Garatachea, Alberto | - |
dc.contributor.author | Suzuki, Tsutomu | - |
dc.contributor.author | Esteller, Manel | - |
dc.date.accessioned | 2021-01-28T07:53:25Z | - |
dc.date.available | 2021-01-28T07:53:25Z | - |
dc.date.issued | 2020-08-25 | - |
dc.identifier.uri | http://hdl.handle.net/2445/173469 | - |
dc.description.abstract | 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. | - |
dc.format.extent | 9 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | National Academy of Sciences | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1073/pnas.2003358117 | - |
dc.relation.ispartof | Proceedings of The National Academy of Sciences of The United States of America, 2020, vol. 117, num. 34, p. 20785-20793 | - |
dc.relation.uri | https://doi.org/10.1073/pnas.2003358117 | - |
dc.rights | cc by (c) Rosselló Tortella et al., 2020 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | - |
dc.source | Articles publicats en revistes (Ciències Fisiològiques) | - |
dc.subject.classification | Càncer colorectal | - |
dc.subject.classification | Epigenètica | - |
dc.subject.other | Colorectal cancer | - |
dc.subject.other | Epigenetics | - |
dc.title | Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 703031 | - |
dc.date.updated | 2021-01-25T08:06:41Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 32778592 | - |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
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Rossello-TortellaM.pdf | 1.95 MB | Adobe PDF | View/Open |
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