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Nature. 2017 Nov 23;551(7681):472-477. doi: 10.1038/nature24482. Epub 2017 Nov 15.

Visualization of chemical modifications in the human 80S ribosome structure.

Natchiar SK1,2,3,4,5, Myasnikov AG1,2,3,4,5, Kratzat H1,2,3,4,5, Hazemann I1,2,3,4,5, Klaholz BP1,2,3,4,5.

Author information

1
Centre for Integrative Biology (CBI), Department of Integrated Structural Biology, IGBMC, CNRS, Inserm, Université de Strasbourg, 1 rue Laurent Fries, 67404 Illkirch, France.
2
Institute of Genetics and of Molecular and Cellular Biology (IGBMC), 1 rue Laurent Fries, Illkirch, France.
3
Centre National de la Recherche Scientifique (CNRS), UMR 7104, Illkirch, France.
4
Institut National de la Santé et de la Recherche Médicale (Inserm), U964, Illkirch, France.
5
Université de Strasbourg, Illkirch, France.

Abstract

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.

PMID:
29143818
DOI:
10.1038/nature24482
[Indexed for MEDLINE]

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