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Universally conserved isoasparylation sustains ribosome biogenesis and function

Bonnettaz, B.; Smirnova, A.; Vayssieres, M.; Delbos, L.; Zelie, E.; Kammoun, Z.; Abou Khalil, Y.; Zhang, M.; Liu, W.-Q.; Vidal, M.; Chicher, J.; Kuhn, L.; Hammann, P.; Alez-Martin, L.; Reinert, T.; Arnaud, N.; Francois, Y.-N.; Blaud, M.; Leulliot, N.; Smirnov, A.

2026-08-27 biochemistry
10.64898/2026.08.26.747345 bioRxiv
Show abstract

All living beings use ribosomes to synthesize proteins from -amino acids. Inherited from our common ancestor, a few universally conserved ribosome biogenesis steps, introducing essential ribosomal RNA modifications, have survived to our days. However, it was unknown whether similar primordial core mechanisms could also target ribosomal proteins. Here we show that the assembly and the function of ribosomes depend on the installation of an unusual {beta}-amino acid, isoaspartate, within the ribosomal protein uS11. In bacteria, mitochondria, and plastids, this modification is catalyzed by the metzincin-like hydrolase YbeY, whereas in archaea and eukaryotes, it is introduced by the atypical kinase Fap7. The formation of this strategically positioned isoaspartate enables correct maturation of the small ribosomal subunit to support protein synthesis and normal cell physiology.

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