1. Biochemistry and Chemical Biology
  2. Structural Biology and Molecular Biophysics
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Distinct and evolutionary conserved structural features of the human nuclear exosome complex

  1. Piotr Gerlach
  2. Jan M Schuller
  3. Fabien Bonneau
  4. Jerome Basquin
  5. Peter Reichelt
  6. Sebastian Falk
  7. Elena Conti  Is a corresponding author
  1. Max Planck Institute of Biochemistry, Germany
Research Article
  • Cited 16
  • Views 2,517
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Cite this article as: eLife 2018;7:e38686 doi: 10.7554/eLife.38686

Abstract

The nuclear RNA exosome complex mediates the processing of structured RNAs and the decay of aberrant non-coding RNAs, an important function particularly in human cells. Most mechanistic studies to date have focused on the yeast system. Here, we reconstituted and studied the properties of a recombinant 14-subunit human nuclear exosome complex. In biochemical assays, the human exosome embeds a longer RNA channel than its yeast counterpart. The 3.8 Å resolution cryo-EM structure of the core complex bound to a single-stranded RNA reveals that the RNA channel path is formed by two distinct features of the hDIS3 exoribonuclease: an open conformation and a domain organization more similar to bacterial RNase II than to yeast Rrp44. The cryo-EM structure of the holo-complex shows how obligate nuclear cofactors position the hMTR4 helicase at the entrance of the core complex, suggesting a striking structural conservation from lower to higher eukaryotes.

Data availability

The cryo-EM density maps are deposited in the Electron Microscopy Data Bank under accession numbers EMD-0127 and EMD-0128. The atomic model is deposited in the Protein Data Bank (PDB) under accession number 6H25.

The following data sets were generated
    1. Schuller JM
    2. Falk S
    3. Basquin J
    4. Conti E
    (2018) Human nuclear RNA exosome EXO-14 complex (cryo-EM density map)
    Publicly available at the Electron Microscopy Data Bank (accession no: EMD-0127).
    1. Schuller JM
    2. Falk S
    3. Basquin J
    4. Conti E
    (2018) Cryo-EM density map
    Publicly available at the Electron Microscopy Data Bank (accession no: EMD-0128).

Article and author information

Author details

  1. Piotr Gerlach

    Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9599-7322
  2. Jan M Schuller

    Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9121-1764
  3. Fabien Bonneau

    Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8787-7662
  4. Jerome Basquin

    Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Martinsried, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Peter Reichelt

    Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Sebastian Falk

    Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7848-4621
  7. Elena Conti

    Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Munich, Germany
    For correspondence
    conti@biochem.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1254-5588

Funding

European Molecular Biology Organization (ALTF 1008-2015)

  • Piotr Gerlach

European Commission (ERC-2016-ADG 740329 EXORICO)

  • Elena Conti

Deutsche Forschungsgemeinschaft (SFB646)

  • Elena Conti

Louis-Jeantet Foundation

  • Elena Conti

Max-Planck-Gesellschaft

  • Elena Conti

Deutsche Forschungsgemeinschaft (SFB1035)

  • Elena Conti

Deutsche Forschungsgemeinschaft (GRK1721)

  • Elena Conti

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Sjors HW Scheres, MRC Laboratory of Molecular Biology, United Kingdom

Publication history

  1. Received: May 26, 2018
  2. Accepted: July 17, 2018
  3. Accepted Manuscript published: July 26, 2018 (version 1)
  4. Version of Record published: August 2, 2018 (version 2)

Copyright

© 2018, Gerlach et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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