Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer

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...

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Autores: Rosselló-Tortella, Margalida|||0000-0003-4610-7981, Llinàs-Arias, Pere|||0000-0002-3666-0532, Sakaguchi, Y., Miyauchi, K., Davalos, Veronica|||0000-0003-4077-5137, Setien, Fernando|||0000-0002-4061-4635, Calleja-Cervantes, María Eréndira|||0000-0003-0688-0793, Piñeyro, David|||0000-0001-5633-3339, Martínez-Gómez, Jesús|||0000-0002-7770-073X, Guil, Sonia|||0000-0002-2257-3331, Joshi, Ricky S.|||0000-0003-4463-0453, Villanueva, Alejandro|||0000-0001-5164-0006, Suzuki, Tsutomu, Esteller, M.|||0000-0003-4490-6093
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:236595
Acceso en línea:https://ddd.uab.cat/record/236595
https://dx.doi.org/urn:doi:10.1073/pnas.2003358117
Access Level:acceso abierto
Palabra clave:Cancer
Epigenetics
Transfer RNA
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spelling Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancerRosselló-Tortella, Margalida|||0000-0003-4610-7981Llinàs-Arias, Pere|||0000-0002-3666-0532Sakaguchi, Y.Miyauchi, K.Davalos, Veronica|||0000-0003-4077-5137Setien, Fernando|||0000-0002-4061-4635Calleja-Cervantes, María Eréndira|||0000-0003-0688-0793Piñeyro, David|||0000-0001-5633-3339Martínez-Gómez, Jesús|||0000-0002-7770-073XGuil, Sonia|||0000-0002-2257-3331Joshi, Ricky S.|||0000-0003-4463-0453Villanueva, Alejandro|||0000-0001-5164-0006Suzuki, TsutomuEsteller, M.|||0000-0003-4490-6093CancerEpigeneticsTransfer RNATransfer 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.Universitat Autònoma de Barcelona 22020-01-0120202020-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/236595https://dx.doi.org/urn:doi:10.1073/pnas.2003358117reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 IFI17-00006Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 RTI2018-094049-B-I00Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 SAF2014-55000Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-1080open accesshttp://purl.org/coar/access_right/c_abf2Aquest 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.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2365952026-06-06T12:50:31Z
dc.title.none.fl_str_mv Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer
title Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer
spellingShingle Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer
Rosselló-Tortella, Margalida|||0000-0003-4610-7981
Cancer
Epigenetics
Transfer RNA
title_short Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer
title_full Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer
title_fullStr Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer
title_full_unstemmed Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer
title_sort Epigenetic loss of the transfer RNA-modifying enzyme TYW2 induces ribosome frameshifts in colon cancer
dc.creator.none.fl_str_mv Rosselló-Tortella, Margalida|||0000-0003-4610-7981
Llinàs-Arias, Pere|||0000-0002-3666-0532
Sakaguchi, Y.
Miyauchi, K.
Davalos, Veronica|||0000-0003-4077-5137
Setien, Fernando|||0000-0002-4061-4635
Calleja-Cervantes, María Eréndira|||0000-0003-0688-0793
Piñeyro, David|||0000-0001-5633-3339
Martínez-Gómez, Jesús|||0000-0002-7770-073X
Guil, Sonia|||0000-0002-2257-3331
Joshi, Ricky S.|||0000-0003-4463-0453
Villanueva, Alejandro|||0000-0001-5164-0006
Suzuki, Tsutomu
Esteller, M.|||0000-0003-4490-6093
author Rosselló-Tortella, Margalida|||0000-0003-4610-7981
author_facet Rosselló-Tortella, Margalida|||0000-0003-4610-7981
Llinàs-Arias, Pere|||0000-0002-3666-0532
Sakaguchi, Y.
Miyauchi, K.
Davalos, Veronica|||0000-0003-4077-5137
Setien, Fernando|||0000-0002-4061-4635
Calleja-Cervantes, María Eréndira|||0000-0003-0688-0793
Piñeyro, David|||0000-0001-5633-3339
Martínez-Gómez, Jesús|||0000-0002-7770-073X
Guil, Sonia|||0000-0002-2257-3331
Joshi, Ricky S.|||0000-0003-4463-0453
Villanueva, Alejandro|||0000-0001-5164-0006
Suzuki, Tsutomu
Esteller, M.|||0000-0003-4490-6093
author_role author
author2 Llinàs-Arias, Pere|||0000-0002-3666-0532
Sakaguchi, Y.
Miyauchi, K.
Davalos, Veronica|||0000-0003-4077-5137
Setien, Fernando|||0000-0002-4061-4635
Calleja-Cervantes, María Eréndira|||0000-0003-0688-0793
Piñeyro, David|||0000-0001-5633-3339
Martínez-Gómez, Jesús|||0000-0002-7770-073X
Guil, Sonia|||0000-0002-2257-3331
Joshi, Ricky S.|||0000-0003-4463-0453
Villanueva, Alejandro|||0000-0001-5164-0006
Suzuki, Tsutomu
Esteller, M.|||0000-0003-4490-6093
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv Cancer
Epigenetics
Transfer RNA
topic Cancer
Epigenetics
Transfer RNA
description 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.
publishDate 2020
dc.date.none.fl_str_mv 2
2020-01-01
2020
2020-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/236595
https://dx.doi.org/urn:doi:10.1073/pnas.2003358117
url https://ddd.uab.cat/record/236595
https://dx.doi.org/urn:doi:10.1073/pnas.2003358117
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 IFI17-00006
Agencia Estatal de Investigación https://doi.org/10.13039/501100011033 RTI2018-094049-B-I00
Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 SAF2014-55000
Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-1080
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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