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Título: | METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer |
Autor: | García-Vílchez, Raquel; Añazco-Guenkova, Ana M. CSIC ORCID; Dietmann, Sabine; López, Judith CSIC ORCID; Morón-Calvente, Virginia; D'Ambrosi, Silvia; Nombela, Paz; Zamacola, Kepa; Mendizábal, Isabel; García-Longarte, Saioa; Zabala-Letona, Amaia; Astobiza, Ianire; Fernández, Sonia; Paniagua, Alejandro; Miguel-López, Borja CSIC; Marchand, Virginie; Alonso-López, Diego; Merkel, Angelika; García-Tuñón, Ignacio CSIC ORCID CVN; Ugalde-Olano, Aitziber; Loizaga-Iriarte, Ana; Lacasa-Viscasillas, Isabel; Unda, Miguel; Azkargorta, Mikel; Elortza, Félix; Bárcena, Laura; Gonzalez-Lopez, Monika; Aransay, Ana M.; Di Domenico, Tomás; Sánchez-Martín, Manuel A.; De Las Rivas, Javier CSIC ORCID CVN ; Guil, Sònia; Motorin, Yuri; Helm, Mark; Pandolfi, Pier Paolo; Carracedo, Arkaitz CSIC ORCID; Blanco, Sandra CSIC ORCID CVN | Palabras clave: | Epitranscriptome RNA modifications Prostate cancer 7-methylguanosine tRNA fragments Tumour microenvironment (TME) Interferon Immune checkpoint blockade |
Fecha de publicación: | 29-jul-2023 | Editor: | BioMed Central | Citación: | Molecular Cancer 22: 119 (2023) | Resumen: | 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 N7-methylguanosine (m7G) transferase METTL1 is highly expressed in primary and advanced prostate tumours. Mechanistically, we find that METTL1 depletion causes the loss of m7G 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 m7G tRNA methylation in cancer cell translation control and tumour biology. | Versión del editor: | https://doi.org/10.1186/s12943-023-01809-8 | URI: | http://hdl.handle.net/10261/347759 | DOI: | 10.1186/s12943-023-01809-8 | E-ISSN: | 1476-4598 |
Aparece en las colecciones: | (IBMCC) Artículos |
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METTL1_García_Art_2023.pdf | 4,83 MB | Adobe PDF | Visualizar/Abrir |
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