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

ABSTRACT: 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 N⁷-guanosine methylation (m⁷G) of tRNAs, mediated by METTL1, regulates survival to stress conditions in cancer cells. Mechanistically, we find that m⁷G in tRNAs protects them from stress-induced cleavage and processing into 5' tRNA fragments. Our analyses reveal that the loss of tRNA m⁷G methylation activates stress response pathways, sensitising cancer cells to stress. Furthermore, we find that the loss of METTL1 r

SUBMITTER: Garcia-Vilchez R 

PROVIDER: S-EPMC10589097 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature