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bioRxiv · 10.1101/2025.03.11.642699

O-GlcNAc modifications regulate lamin A tail processing

Augspurger, K. R.·Martin, E. A.·Maynard, J.·Welle, K.·Ghaemmaghami, S.·Burlingame, A.·Panning, B.·Buchwalter, A.
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Abstract

Lamin A processing is highly regulated, and necessary for proper assembly of the nuclear lamina facilitating its role in nuclear structure and chromatin organization. Pre-lamin A is first farnesylated, and then a short C-terminal peptide is cleaved to produce mature lamin A. O-GlcNAc Transferase (OGT), a glucose sensitive post-translational modification enzyme, is a potential regulator for lamin A processing. To explore the role of OGT in lamin A biogenesis, we examined the effects of OGT levels and OGT inhibition. Variation in OGT dose or inhibition of its activity did not alter endogenous lamin A abundance or distribution. To more directly test the regulatory effects of O-GlcNAcylation on lamin A, we adapted a tail cleavage assay. Mutation of an OGT binding motif and O-GlcNAc modification sites reduced tail cleavage efficiency, suggesting that O-GlcNAcylation promotes lamin A processing. Our findings add to the understanding of the regulation of lamin A cleavage and identify a potential link between glucose metabolism and lamina biogenesis.

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Augspurger, K. R., Martin, E. A., Maynard, J., Welle, K., Ghaemmaghami, S., Burlingame, A., Panning, B., Buchwalter, A.. 2025-03-13. O-GlcNAc modifications regulate lamin A tail processing. https://doi.org/10.1101/2025.03.11.642699

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