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The tRNA methyltransferase METTL6 requires seryl-tRNA synthetase for tRNASer targeting

Nature Structural & Molecular Biology (2024)Cite this article

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Overexpression of the RNA methyltransferase METTL6 leads to increased proliferation and promotes cancer. Our cryo-electron microscopy (cryo-EM) and biochemical analyses reveal that METTL6 requires seryl-tRNA synthetase as a cofactor to efficiently generate 3-methyl-cytosine in serine tRNAs.

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Fig. 1: The METTL6–SerRS–tRNASer complex.

References

  1. Xu, L. et al. Three distinct 3-methylcytidine (m3C) methyltransferases modify tRNA and mRNA in mice and humans. J. Biol. Chem. 292, 14695–14703 (2017). This paper reports the discovery of three mammalian m3C methyltransferases.

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  2. Bohnsack, K. E., Kleiber, N., Lemus-Diaz, N. & Bohnsack, M. T. Roles and dynamics of 3-methylcytidine in cellular RNAs. Trends Biochem. Sci. 47, 596–608 (2022). A review article about m3C modification.

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  4. Mao, X.-L. et al. Mutually exclusive substrate selection strategy by human m3C RNA transferases METTL2A and METTL6. Nucleic Acids Res. 49, 8309–8323 (2021). This paper compares substrate specificities of the cytosolic m3C methyltransferases METTL6 and METTL2.

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This is a summary of: Throll, P. et al. Structural basis of tRNA recognition by the m3C RNA methyltransferase METTL6 in complex with SerRS seryl-tRNA synthetase. Nat. Struct. Mol. Biol. https://doi.org/10.1038/s41594-024-01341-3 (2024).

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The tRNA methyltransferase METTL6 requires seryl-tRNA synthetase for tRNASer targeting. Nat Struct Mol Biol (2024). https://doi.org/10.1038/s41594-024-01343-1

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