guest ::
| Home > Articles > Published articles > METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer |
| Home > Articles > Published articles > METTL1 promotes tumorigenesis through tRNA-derived fragment biogenesis in prostate cancer |
(Centro de Investigación Biomédica en Red de Cáncer) (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras) (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas) (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas) (Johannes Gutenberg-University Mainz, Germany) (Centro de Investigación Biomédica en Red de Cáncer)| Date: | 2023 |
| Abstract: | 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. |
| Grants: | Agencia Estatal de Investigación PID2019-111692RB-I00 Ministerio de Economía y Competitividad RYC-2014-16550 Agencia Estatal de Investigación PID2019-108787RB-I00 European Commission. Horizon 2020 819242 |
| Rights: | Aquest 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.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Epitranscriptome ; RNA modifcations ; Prostate cancer ; 7-methylguanosine ; Trna fragments ; Tumour microenvironment (TME) ; Interferon ; Immune checkpoint blockade |
| Published in: | Molecular cancer, Vol. 22 Núm. 1 (july 2023) , ISSN 1476-4598 |
