TY - JOUR
T1 - N7-methylguanosine methylation of tRNAs regulates survival to stress in cancer
AU - García-Vílchez, Raquel
AU - Añazco-Guenkova, Ana M.
AU - López, Judith
AU - Dietmann, Sabine
AU - Tomé, Mercedes
AU - Jimeno, Sonia
AU - Azkargorta, Mikel
AU - Elortza, Félix
AU - Bárcena, Laura
AU - Gonzalez-Lopez, Monika
AU - Aransay, Ana M.
AU - Sánchez-Martín, Manuel A.
AU - Huertas, Pablo
AU - Durán, Raúl V.
AU - Blanco, Sandra
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/10/20
Y1 - 2023/10/20
N2 - 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 reduces tumour growth and increases cytotoxic stress 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 chemotherapy.
AB - 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 reduces tumour growth and increases cytotoxic stress 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 chemotherapy.
UR - http://www.scopus.com/inward/record.url?scp=85169606228&partnerID=8YFLogxK
U2 - 10.1038/s41388-023-02825-0
DO - 10.1038/s41388-023-02825-0
M3 - Article
C2 - 37660182
AN - SCOPUS:85169606228
SN - 0950-9232
VL - 42
SP - 3169
EP - 3181
JO - Oncogene
JF - Oncogene
IS - 43
ER -