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RNA modification

O-GlcNAc regulates YTHDF1 and YTHDF3 activity

Nature Cell Biology volume 25, pages 1570–1572 (2023)Cite this article

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YTHDF family members are ‘readers’ of a common mRNA modification, but their effects on mRNA translation and stability have been disputed. A new study shows that YTHDF1 and YTHDF3 are post-translationally regulated through O-GlcNAcylation, unifying disparate results and pointing to environmental cues that could modulate YTHDF function.

N6-methyladenosine (m6A) is a highly regulated mRNA modification that directs gene expression for many essential biological processes1. Proteins that recognize the m6A modification and mediate its biological effects are referred to as readers. A family of m6A readers that contain YT521-B homology (YTH) domains has been implicated in regulation of mRNA translation and stability, but studies in different cell lines yielded contradictory findings. In this issue of Nature Cell Biology, Chen et al.2 report that the O-GlcNAc post-translational modification (PTM) regulates the translation-promoting activity of two YTH domain proteins, elucidating an unrecognized facet of m6A biology and reconciling previously incongruous results.

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Fig. 1: O-GlcNAcylation regulates YTHDF1/3 function.

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Acknowledgements

We thank Y. Nam for comments on the manuscript.

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  1. Department of Biochemistry, UT Southwestern, Dallas, TX, USA

    Mary W. N. Burns & Jennifer J. Kohler

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  1. Mary W. N. Burns
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  2. Jennifer J. Kohler
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Correspondence to Jennifer J. Kohler.

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Burns, M.W.N., Kohler, J.J. O-GlcNAc regulates YTHDF1 and YTHDF3 activity. Nat Cell Biol 25, 1570–1572 (2023). https://doi.org/10.1038/s41556-023-01275-w

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