Cryo-EM structure of the naked mole-rat ribosome reveals a stabilized split 28S rRNA

<h4>ABSTRACT</h4> The naked mole-rat (Heterocephalus glaber) is a long-lived mammal with remarkable resistance to cancer and hypoxia, suggesting the evolution of robust proteostasis(definition) networks. The ribosome, the central engine of protein synthesis, is key for cellular stress responses and has an unusual feature of 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 two 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 unique 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 nearly indistinguishable from intact mouse and human ribosomes. These findings resolve the structural basis of this unique 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.