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Localization-dictated function for METTL3

Nature Cell Biology volume 24, pages 1188–1189 (2022)Cite this article

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Aberrant subcellular localization of proteins contributes to the pathogenesis of cancer. A study now reports that the mis-localization of METTL3, a nuclear N6-adenosine methyltransferase, to the cytoplasm promotes gastric cancer by enhancing mRNA translation of a subset of oncogenes, independently of the N6-methyladenosine (m6A) modification.

In this issue of Nature Cell Biology, Wei et al.5 report novel methylation-independent functions of METTL3 in the cytoplasm whereby METTL3 promotes stomach cancer via upregulation of mRNA translation of specific transcripts. Overexpression of METTL3 in gastric cancer correlated with poor prognosis of patients and suppression of METTL3 reduced patient-derived xenograft tumorigenicity in vivo. In most cancer studies, overexpression of METTL3 correlates with increased m6A levels and has pro-oncogenic roles4, and, as expected, the authors identified many METTL3-mediated m6A sites in human gastric cancer cell lines locating to 3′ untranslated regions (UTRs) near stop codons. However, less than 5% of all METTL3-bound mRNAs overlapped with m6A sites. Binding of METTL3 to non-modified mRNAs is probably not surprising given that METTL3 functions as a methyltransferase and m6A itself is detected by specific reader proteins. However, the substantial number of mRNAs interacting with METTL3 in the 3′-untranslated region that did not carry m6A prompted the question of whether METTL3 displayed additional methylation-independent functions specific to gastric cancer.

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Fig. 1: METTL3 has different functions depending on its subcellular location in gastric cancer.

References

  1. He, P. C. & He, C. EMBO J. 40, e105977 (2021).

    CAS  Article  Google Scholar 

  2. Choe, J. et al. Nature 561, 556–560 (2018).

    CAS  Article  Google Scholar 

  3. Lin, S., Choe, J., Du, P., Triboulet, R. & Gregory, R. I. Mol. Cell 62, 335–345 (2016).

    CAS  Article  Google Scholar 

  4. Zheng, W. et al. Front. Oncol. 9, 1403 (2019).

    Article  Google Scholar 

  5. Wei, X. et al. Nat. Cell Biol. https://doi.org/10.1038/s41556-022-00968-y (2022).

  6. Wang, P., Doxtader, K. A. & Nam, Y. Mol. Cell 63, 306–317 (2016).

    CAS  Article  Google Scholar 

  7. Raj, N. et al. Mol. Cell 82, P2370–2384.E10 (2022).

    Article  Google Scholar 

  8. Kandoth, C. et al. Nature 502, 333–339 (2013).

    CAS  Article  Google Scholar 

  9. Coots, R. A. et al. Mol. Cell 68, 504–514.e7 (2017).

    CAS  Article  Google Scholar 

  10. Gray, N. K., Hrabalkova, L., Scanlon, J. P. & Smith, R. W. Biochem. Soc. Trans. 43, 1277–1284 (2015).

    CAS  Article  Google Scholar 

  11. Wells, S. E., Hillner, P. E., Vale, R. D. & Sachs, A. B. Mol. Cell 2, 135–140 (1998).

    CAS  Article  Google Scholar 

  12. Schutz, P. et al. Proc. Natl Acad. Sci. USA 105, 9564–9569 (2008).

    CAS  Article  Google Scholar 

Download references

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  1. German Cancer Research Center – Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany

    Sylvain Delaunay & Michaela Frye

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  1. Sylvain Delaunay
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  2. Michaela Frye
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Correspondence to Michaela Frye.

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M.F. receives commercial funding from MERCK. S.D. declares no competing interests.

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Delaunay, S., Frye, M. Localization-dictated function for METTL3. Nat Cell Biol 24, 1188–1189 (2022). https://doi.org/10.1038/s41556-022-00972-2

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