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)...

Descripción completa

Detalles Bibliográficos
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
Descripción
Sumario: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.

Similares en LA Referencia