Universally conserved isoasparylation sustains ribosome biogenesis and function

Bruno Bonnettaz; Anna Smirnova; Marlène Vayssières; Lila Delbos; Emilie Zélie; Zaineb Fourati; Yelda Abou Khalil; Mengmeng Zhang; Wang‐Qing Liu; Michel Vidal; Johana Chicher; Lauriane Kühn; Philippe Hammann; Lola Alez-Martin; Tessa Reinert; Nicolas Arnaud; Yannis‐Nicolas François; Magali Blaud; Nicolas Leulliot; Alexandre Smirnov

doi:10.64898/2026.08.26.747345

BiochemistrybioRxivAug 27, 2026

Preprint

Universally conserved isoasparylation sustains ribosome biogenesis and function

Bruno Bonnettaz iD, Anna Smirnova iD, Marlène Vayssières iD, Lila Delbos iD, Emilie Zélie iD, Zaineb Fourati iD, Yelda Abou Khalil iD, Mengmeng Zhang, Wang‐Qing Liu iD, Michel Vidal iD, Johana Chicher iD, Lauriane Kühn iD, Philippe Hammann iD, Lola Alez-Martin iD, Tessa Reinert iD, Nicolas Arnaud iD, Yannis‐Nicolas François iD, Magali Blaud iD, Nicolas Leulliot iD, Alexandre Smirnov iD

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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