Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 551 (7681), 472-477

Visualization of Chemical Modifications in the Human 80S Ribosome Structure

Affiliations

Visualization of Chemical Modifications in the Human 80S Ribosome Structure

S Kundhavai Natchiar et al. Nature.

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.

Comment in

Similar articles

See all similar articles

Cited by 41 articles

See all "Cited by" articles

References

    1. Biomedica. 2014 Apr;34 Suppl 1:41-9 - PubMed
    1. J Mol Biol. 2009 May 29;389(1):146-56 - PubMed
    1. RNA. 2014 Oct;20(10):1632-44 - PubMed
    1. Mol Biol Cell. 2015 Jun 1;26(11):2080-95 - PubMed
    1. Nucleic Acids Res. 2016 Oct 14;44(18):8897-8907 - PubMed

LinkOut - more resources

Feedback