METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer

Newly growing evidence highlights the essential role that epitranscriptomic marks play in the development of many cancers; however, little is known about the role and implications of altered epitranscriptome deposition in prostate cancer. Here, we show that the transfer RNA N-7-methylguanosine (m(7)...

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Autores: García Vílchez, Raquel, Añazco Guenkova, Ana Macrina, Dietmann, Sabine, Lopez, Judith, Morón Calvente, Virginia, D'Ambrosi, Silvia, Nombela, Paz, Zamacola, Kepa, Mendizabal, Isabel, García Longarte, Saioa, Zabala Letona, Amaia, Astobiza, Ianire, Fernández, Sonia, Paniagua, Alejandro, Miguel López, Borja, Marchand, Virginie, Alonso López, Diego, Merkel, Angelika, García Tuñón Llanio, Ignacio|||0000-0003-4758-2151, Azkargorta, Mikel, Elortza, Félix, Bárcena, Laura, González López, Monika, Aransay, Ana M., Di Domenico, Tomás, Sanchez Martin, Manuel, Rivas, Javier de las, Guil, Sònia, Motorin, Yuri, Helm, Mark, Pandolfi, Pier Paolo, Carracedo, Arkaitz, Blanco, Sandra
Tipo de recurso: artículo
Fecha de publicación:2023
País:España
Institución:Universidad de Alcalá (UAH)
Repositorio:e_Buah Biblioteca Digital Universidad de Alcalá
Idioma:inglés
OAI Identifier:oai:ebuah.uah.es:10017/60488
Acceso en línea:http://hdl.handle.net/10017/60488
https://dx.doi.org/10.1186/s12943-023-01809-8
Access Level:acceso abierto
Palabra clave:Epitranscriptome
RNA modifications
Prostate cancer
7-methylguanosinet
RNA fragments
Tumour microenvironment (TME)
InterferonImmune checkpoint blockade
Medicina
Medicine
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network_acronym_str ES
network_name_str España
repository_id_str
spelling METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancerGarcía Vílchez, RaquelAñazco Guenkova, Ana MacrinaDietmann, SabineLopez, JudithMorón Calvente, VirginiaD'Ambrosi, SilviaNombela, PazZamacola, KepaMendizabal, IsabelGarcía Longarte, SaioaZabala Letona, AmaiaAstobiza, IanireFernández, SoniaPaniagua, AlejandroMiguel López, BorjaMarchand, VirginieAlonso López, DiegoMerkel, AngelikaGarcía Tuñón Llanio, Ignacio|||0000-0003-4758-2151Azkargorta, MikelElortza, FélixBárcena, LauraGonzález López, MonikaAransay, Ana M.Di Domenico, TomásSanchez Martin, ManuelRivas, Javier de lasGuil, SòniaMotorin, YuriHelm, MarkPandolfi, Pier PaoloCarracedo, ArkaitzBlanco, SandraEpitranscriptomeRNA modificationsProstate cancer7-methylguanosinetRNA fragmentsTumour microenvironment (TME)InterferonImmune checkpoint blockadeMedicinaMedicineNewly growing evidence highlights the essential role that epitranscriptomic marks play in the development of many cancers; however, little is known about the role and implications of altered epitranscriptome deposition in prostate cancer. Here, we show that the transfer RNA N-7-methylguanosine (m(7)G) transferase METTL1 is highly expressed in primary and advanced prostate tumours. Mechanistically, we find that METTL1 depletion causes the loss of m(7)G tRNA methylation and promotes the biogenesis of a novel class of small non-coding RNAs derived from 5'tRNA fragments. 5'tRNA-derived small RNAs steer translation control to favour the synthesis of key regulators of tumour growth suppression, interferon pathway, and immune effectors. Knockdown of Mettl1 in prostate cancer preclinical models increases intratumoural infiltration of pro-inflammatory immune cells and enhances responses to immunotherapy. Collectively, our findings reveal a therapeutically actionable role of METTL1-directed m(7)G tRNA methylation in cancer cell translation control and tumour biology.20232023-07-29journal articlehttp://purl.org/coar/resource_type/c_6501NAhttp://purl.org/coar/version/c_be7fb7dd8ff6fe43info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10017/60488https://dx.doi.org/10.1186/s12943-023-01809-8reponame:e_Buah Biblioteca Digital Universidad de Alcaláinstname:Universidad de Alcalá (UAH)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ebuah.uah.es:10017/604882026-06-18T11:13:07Z
dc.title.none.fl_str_mv METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer
title METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer
spellingShingle METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer
García Vílchez, Raquel
Epitranscriptome
RNA modifications
Prostate cancer
7-methylguanosinet
RNA fragments
Tumour microenvironment (TME)
InterferonImmune checkpoint blockade
Medicina
Medicine
title_short METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer
title_full METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer
title_fullStr METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer
title_full_unstemmed METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer
title_sort METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer
dc.creator.none.fl_str_mv García Vílchez, Raquel
Añazco Guenkova, Ana Macrina
Dietmann, Sabine
Lopez, Judith
Morón Calvente, Virginia
D'Ambrosi, Silvia
Nombela, Paz
Zamacola, Kepa
Mendizabal, Isabel
García Longarte, Saioa
Zabala Letona, Amaia
Astobiza, Ianire
Fernández, Sonia
Paniagua, Alejandro
Miguel López, Borja
Marchand, Virginie
Alonso López, Diego
Merkel, Angelika
García Tuñón Llanio, Ignacio|||0000-0003-4758-2151
Azkargorta, Mikel
Elortza, Félix
Bárcena, Laura
González López, Monika
Aransay, Ana M.
Di Domenico, Tomás
Sanchez Martin, Manuel
Rivas, Javier de las
Guil, Sònia
Motorin, Yuri
Helm, Mark
Pandolfi, Pier Paolo
Carracedo, Arkaitz
Blanco, Sandra
author García Vílchez, Raquel
author_facet García Vílchez, Raquel
Añazco Guenkova, Ana Macrina
Dietmann, Sabine
Lopez, Judith
Morón Calvente, Virginia
D'Ambrosi, Silvia
Nombela, Paz
Zamacola, Kepa
Mendizabal, Isabel
García Longarte, Saioa
Zabala Letona, Amaia
Astobiza, Ianire
Fernández, Sonia
Paniagua, Alejandro
Miguel López, Borja
Marchand, Virginie
Alonso López, Diego
Merkel, Angelika
García Tuñón Llanio, Ignacio|||0000-0003-4758-2151
Azkargorta, Mikel
Elortza, Félix
Bárcena, Laura
González López, Monika
Aransay, Ana M.
Di Domenico, Tomás
Sanchez Martin, Manuel
Rivas, Javier de las
Guil, Sònia
Motorin, Yuri
Helm, Mark
Pandolfi, Pier Paolo
Carracedo, Arkaitz
Blanco, Sandra
author_role author
author2 Añazco Guenkova, Ana Macrina
Dietmann, Sabine
Lopez, Judith
Morón Calvente, Virginia
D'Ambrosi, Silvia
Nombela, Paz
Zamacola, Kepa
Mendizabal, Isabel
García Longarte, Saioa
Zabala Letona, Amaia
Astobiza, Ianire
Fernández, Sonia
Paniagua, Alejandro
Miguel López, Borja
Marchand, Virginie
Alonso López, Diego
Merkel, Angelika
García Tuñón Llanio, Ignacio|||0000-0003-4758-2151
Azkargorta, Mikel
Elortza, Félix
Bárcena, Laura
González López, Monika
Aransay, Ana M.
Di Domenico, Tomás
Sanchez Martin, Manuel
Rivas, Javier de las
Guil, Sònia
Motorin, Yuri
Helm, Mark
Pandolfi, Pier Paolo
Carracedo, Arkaitz
Blanco, Sandra
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Epitranscriptome
RNA modifications
Prostate cancer
7-methylguanosinet
RNA fragments
Tumour microenvironment (TME)
InterferonImmune checkpoint blockade
Medicina
Medicine
topic Epitranscriptome
RNA modifications
Prostate cancer
7-methylguanosinet
RNA fragments
Tumour microenvironment (TME)
InterferonImmune checkpoint blockade
Medicina
Medicine
description Newly growing evidence highlights the essential role that epitranscriptomic marks play in the development of many cancers; however, little is known about the role and implications of altered epitranscriptome deposition in prostate cancer. Here, we show that the transfer RNA N-7-methylguanosine (m(7)G) transferase METTL1 is highly expressed in primary and advanced prostate tumours. Mechanistically, we find that METTL1 depletion causes the loss of m(7)G tRNA methylation and promotes the biogenesis of a novel class of small non-coding RNAs derived from 5'tRNA fragments. 5'tRNA-derived small RNAs steer translation control to favour the synthesis of key regulators of tumour growth suppression, interferon pathway, and immune effectors. Knockdown of Mettl1 in prostate cancer preclinical models increases intratumoural infiltration of pro-inflammatory immune cells and enhances responses to immunotherapy. Collectively, our findings reveal a therapeutically actionable role of METTL1-directed m(7)G tRNA methylation in cancer cell translation control and tumour biology.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-07-29
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
NA
http://purl.org/coar/version/c_be7fb7dd8ff6fe43
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10017/60488
https://dx.doi.org/10.1186/s12943-023-01809-8
url http://hdl.handle.net/10017/60488
https://dx.doi.org/10.1186/s12943-023-01809-8
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/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
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:e_Buah Biblioteca Digital Universidad de Alcalá
instname:Universidad de Alcalá (UAH)
instname_str Universidad de Alcalá (UAH)
reponame_str e_Buah Biblioteca Digital Universidad de Alcalá
collection e_Buah Biblioteca Digital Universidad de Alcalá
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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