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N7-methylguanosine methylation of tRNAs regulates survival to stress in cancer

ABSTRACT: Combining transcriptome-wide approaches to detect m7G RNA methylation, in vitro functional assays and Mettl1 knockout mouse models, we provide evidence that guanosine-7 tRNA methylation is required to protect tRNAs from cleavage in response to stress, leading to impaired regulation of protein synthesis. Loss of METTL1 and tRNA methylation sensitises cancer cells to stress, reducing tumour growth and increasing cytotoxic responses to convectional cancer treatments in vitro and in vivo. Our study uncovers the role of m7G methylation of tRNAs in stress responses and highlights the potential of targeting METTL1 to sensitise cancer cells to therapy.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Mus Musculus (mouse)

DISEASE(S): Prostate Adenocarcinoma

SUBMITTER: Mikel Azkargorta

LAB HEAD: Felix Elortza

PROVIDER: PXD036009 | Pride | 2024-01-26

REPOSITORIES: Pride

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N7-methylguanosine methylation of tRNAs regulates survival to stress in cancer.

García-Vílchez Raquel R Añazco-Guenkova Ana M AM López Judith J Dietmann Sabine S Tomé Mercedes M Jimeno Sonia S Azkargorta Mikel M Elortza Félix F Bárcena Laura L Gonzalez-Lopez Monika M Aransay Ana M AM Sánchez-Martín Manuel A MA Huertas Pablo P Durán Raúl V RV Blanco Sandra S

Oncogene 20230902 43

Tumour progression and therapy tolerance are highly regulated and complex processes largely dependent on the plasticity of cancer cells and their capacity to respond to stress. The higher plasticity of cancer cells highlights the need for identifying targetable molecular pathways that challenge cancer cell survival. Here, we show that N<sup>7</sup>-guanosine methylation (m<sup>7</sup>G) of tRNAs, mediated by METTL1, regulates survival to stress conditions in cancer cells. Mechanistically, we fin ...[more]

PMID: 37660182

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