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

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.