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Visualization of chemical modifications in the human 80S ribosome structure

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  • S. Kundhavai Natchiar

    (Centre for Integrative Biology (CBI), IGBMC, CNRS, Inserm, Université de Strasbourg
    Institute of Genetics and of Molecular and Cellular Biology (IGBMC)
    Centre National de la Recherche Scientifique (CNRS)
    Institut National de la Santé et de la Recherche Médicale (Inserm))

  • Alexander G. Myasnikov

    (Centre for Integrative Biology (CBI), IGBMC, CNRS, Inserm, Université de Strasbourg
    Institute of Genetics and of Molecular and Cellular Biology (IGBMC)
    Centre National de la Recherche Scientifique (CNRS)
    Institut National de la Santé et de la Recherche Médicale (Inserm))

  • Hanna Kratzat

    (Centre for Integrative Biology (CBI), IGBMC, CNRS, Inserm, Université de Strasbourg
    Institute of Genetics and of Molecular and Cellular Biology (IGBMC)
    Centre National de la Recherche Scientifique (CNRS)
    Institut National de la Santé et de la Recherche Médicale (Inserm))

  • Isabelle Hazemann

    (Centre for Integrative Biology (CBI), IGBMC, CNRS, Inserm, Université de Strasbourg
    Institute of Genetics and of Molecular and Cellular Biology (IGBMC)
    Centre National de la Recherche Scientifique (CNRS)
    Institut National de la Santé et de la Recherche Médicale (Inserm))

  • Bruno P. Klaholz

    (Centre for Integrative Biology (CBI), IGBMC, CNRS, Inserm, Université de Strasbourg
    Institute of Genetics and of Molecular and Cellular Biology (IGBMC)
    Centre National de la Recherche Scientifique (CNRS)
    Institut National de la Santé et de la Recherche Médicale (Inserm))

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.

Suggested Citation

  • S. Kundhavai Natchiar & Alexander G. Myasnikov & Hanna Kratzat & Isabelle Hazemann & Bruno P. Klaholz, 2017. "Visualization of chemical modifications in the human 80S ribosome structure," Nature, Nature, vol. 551(7681), pages 472-477, November.
    • Handle: RePEc:nat:nature:v:551:y:2017:i:7681:d:10.1038_nature24482
    DOI: 10.1038/nature24482
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