Journal: Nat Commun / Year: 2026 Title: Cryo-EM structure of the naked mole-rat ribosome reveals a stabilized split 28S rRNA. Authors: Mehmet Gül / Alice Rossi / Christian M T Spahn / Gary R Lewin / Mikhail Kudryashev / Abstract: The naked mole-rat (Heterocephalus glaber) is a long-lived mammal with resistance to cancer and hypoxia, suggesting the evolution of robust proteostasis networks. The ribosome, central for protein ...The naked mole-rat (Heterocephalus glaber) is a long-lived mammal with resistance to cancer and hypoxia, suggesting the evolution of robust proteostasis networks. The ribosome, central for protein synthesis, is key to cellular stress responses and has an unusual feature: the 28S rRNA split; however, the details of its organization remain unknown. Here, we present high-resolution cryo-EM structures of the naked mole-rat 80S ribosome in four states of the elongation cycle. The structures reveal a conserved overall architecture and rRNA modification landscape compared to other mammals, and provide an atomic-level view of the distinct break in the 28S rRNA. This cleavage event, located in the D6 expansion segment, is structurally stabilized by a network of interactions with surrounding ribosomal proteins, maintaining the integrity of the large subunit. Our comparative analysis revealed that this compensatory network preserves a canonical architecture that is nearly indistinguishable from intact mouse and human ribosomes. These findings resolve the structural basis of this distinct cleavage, showing that it is a stable, integrated feature whose function is likely linked to more subtle regulatory mechanisms, rather than inducing major structural rearrangements.
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