tRNA Modifying Enzymes, NSUN2 and METTL1, Determine Sensitivity to 5-Fluorouracil in HeLa Cells

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The cellular mechanisms for sensing and responding to stress on nucleic acid metabolism or to genotoxic stress are the fundamental and ancient evolutionary biological activities with conserved and diverse biological functions. In yeast, hypomodified mature tRNA species are rapidly decayed under heat stress by the RTD pathway. Yet, it has been shown that tRNA-specific methyltransferases Trm4 and Trm8 protect from tRNA decay. 5-FU, a pyrimidine analog used for cancer treatment, is generally known to act as a thymidylate synthase inhibitor although other ways for the mechanisms of action are suggested. We studied NSUN2 and METTL1, the human orthologs of Trm4 and Trm8 in yeast, and demonstrated that these RTD-related tRNA modifying enzymes are involved in 5-FU sensitivity in cervical cancer HeLa cells. We conclude that the evolutionarily conserved regulation of tRNA modifications is a potential mechanism of chemotherapy resistance in cancer cells.

Vyšlo v časopise: tRNA Modifying Enzymes, NSUN2 and METTL1, Determine Sensitivity to 5-Fluorouracil in HeLa Cells. PLoS Genet 10(9): e32767. doi:10.1371/journal.pgen.1004639
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004639

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