Visualization of chemical modifications in the human 80S ribosome structure.
Fiche publication
Date publication
novembre 2017
Journal
Nature
Auteurs
Membres identifiés du Cancéropôle Est :
Dr KLAHOLZ Bruno
Tous les auteurs :
Natchiar SK, Myasnikov AG, Kratzat H, Hazemann I, Klaholz BP
Lien Pubmed
Résumé
Chemical modifications of human ribosomal RNA (rRNA) are introduced during biogenesis and have been implicated in the dysregulation of protein synthesis, as is found in cancer and other diseases. However, their role in this phenomenon is unknown. Here we visualize more than 130 individual rRNA modifications in the three-dimensional structure of the human ribosome, explaining their structural and functional roles. In addition to a small number of universally conserved sites, we identify many eukaryote- or human-specific modifications and unique sites that form an extended shell in comparison to bacterial ribosomes, and which stabilize the RNA. Several of the modifications are associated with the binding sites of three ribosome-targeting antibiotics, or are associated with degenerate states in cancer, such as keto alkylations on nucleotide bases reminiscent of specialized ribosomes. This high-resolution structure of the human 80S ribosome paves the way towards understanding the role of epigenetic rRNA modifications in human diseases and suggests new possibilities for designing selective inhibitors and therapeutic drugs.
Mots clés
Binding Sites, Cryoelectron Microscopy, Epistasis, Genetic, HeLa Cells, Humans, Ligands, Models, Molecular, RNA Stability, RNA, Ribosomal, biosynthesis, Ribosome Subunits, Large, Eukaryotic, genetics, Ribosome Subunits, Small, Eukaryotic, genetics, Ribosomes, chemistry
Référence
Nature. 2017 11 23;551(7681):472-477