A CRISPR dropout screen for tRNA regulators identified YRDC as the top essential gene in glioblastoma stem cells. Threonine acts as a substrate of YRDC to facilitate the N6-threonylcarbamoyladenosine (t6A) tRNA modification and shift translation toward mitosis-related genes with a codon bias. Our findings support targeting glioblastoma growth by a well-tolerated dietary therapy.
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References
Gimple, R. C., Yang, K., Halbert, M. E., Agnihotri, S. & Rich, J. N. Brain cancer stem cells: resilience through adaptive plasticity and hierarchical heterogeneity. Nat. Rev. Cancer 22, 497–514 (2022). A review article that provides a comprehensive overview of the biology of brain cancer stem cells.
Suzuki, T. The expanding world of tRNA modifications and their disease relevance. Nat. Rev. Mol. Cell Biol. 22, 375–392 (2021). A review article that presents tRNA modifications and their roles in human diseases.
Dedon, P. C. & Begley, T. J. Dysfunctional tRNA reprogramming and codon-biased translation in cancer. Trends Mol. Med. 28, 964–978 (2022). A review article that presents dysregulation of tRNA epitranscriptome and codon-biased translation in cancer.
Yuan, H. et al. Lysine catabolism reprograms tumour immunity through histone crotonylation. Nature 617, 818–826 (2023). In this previous study from our group, we used dietary lysine restriction to reshape the immune microenvironment of GBM.
Lin, H. et al. CO2-sensitive tRNA modification associated with human mitochondrial disease. Nat. Commun. 9, 1875 (2018). This paper reports that mitochondrial t6A formation is dynamically regulated by CO2/bicarbonate.
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This is a summary of: Wu, X. et al. Threonine fuels glioblastoma through YRDC-mediated codon-biased translational reprogramming. Nat. Cancer https://doi.org/10.1038/s43018-024-00748-7 (2024).
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Threonine fuels brain tumor growth through a conserved tRNA modification. Nat Cancer (2024). https://doi.org/10.1038/s43018-024-00750-z
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DOI: https://doi.org/10.1038/s43018-024-00750-z
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