Structure of the human core transcription-export complex reveals a hub for multivalent interactions

  1. Thomas Pühringer
  2. Ulrich Hohmann
  3. Laura Fin
  4. Belén Pacheco-Fiallos
  5. Ulla Schellhaas
  6. Julius Brennecke
  7. Clemens Plaschka  Is a corresponding author
  1. Research Institute of Molecular Pathology (IMP), Austria
  2. Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Austria

Abstract

The export of mRNA from nucleus to cytoplasm requires the conserved and essential transcription and export (TREX) complex (THO–UAP56/DDX39B–ALYREF). TREX selectively binds mRNA maturation marks and licenses mRNA for nuclear export by loading the export factor NXF1–NXT1. How TREX integrates these marks and achieves high selectivity for mature mRNA is poorly understood. Here we report the cryo-electron microscopy structure of the human THO–UAP56/DDX39B complex at 3.3 Å resolution. The seven-subunit THO–UAP56/DDX39B complex multimerizes into a 28-subunit tetrameric assembly, suggesting that selective recognition of mature mRNA is facilitated by the simultaneous sensing of multiple, spatially distant mRNA regions and maturation marks. Two UAP56/DDX39B RNA helicases are juxtaposed at each end of the tetramer, which would allow one bivalent ALYREF protein to bridge adjacent helicases and regulate the TREX–mRNA interaction. Our structural and biochemical results suggest a conserved model for TREX complex function that depends on multivalent interactions between proteins and mRNA.

Data availability

Three-dimensional cryo-EM density maps A, B, C, D, and E have been deposited in the Electron Microscopy Data Bank under the accession numbers EMD-11853, EMD-11857, EMD-11854, EMD-11855, EMD-11856, respectively. The coordinate file of the human THO-UAP56 complex has been deposited in the Protein Data Bank under the accession number 7APK.

The following data sets were generated

Article and author information

Author details

  1. Thomas Pühringer

    Research Institute of Molecular Pathology (IMP), Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9127-9120
  2. Ulrich Hohmann

    Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2124-1439
  3. Laura Fin

    Research Institute of Molecular Pathology (IMP), Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  4. Belén Pacheco-Fiallos

    Research Institute of Molecular Pathology (IMP), Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  5. Ulla Schellhaas

    Research Institute of Molecular Pathology (IMP), Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9684-9839
  6. Julius Brennecke

    Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria
    Competing interests
    The authors declare that no competing interests exist.
  7. Clemens Plaschka

    Research Institute of Molecular Pathology (IMP), Vienna, Austria
    For correspondence
    clemens.plaschka@imp.ac.at
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6020-9514

Funding

Boehringer Ingelheim

  • Clemens Plaschka

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (P2GEP3_188343)

  • Ulrich Hohmann

H2020 European Research Council (ERC-2015-CoG 682181)

  • Julius Brennecke

Austrian Science Fund (F4303 and W1207)

  • Julius Brennecke

Österreichischen Akademie der Wissenschaften

  • Julius Brennecke

H2020 European Research Council (ERC-2020-STG 949081)

  • Clemens Plaschka

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

Reviewing Editor

  1. Karsten Weis, ETH Zurich, Switzerland

Publication history

  1. Received: July 28, 2020
  2. Accepted: November 13, 2020
  3. Accepted Manuscript published: November 16, 2020 (version 1)
  4. Version of Record published: December 16, 2020 (version 2)

Copyright

© 2020, Pühringer 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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  1. Thomas Pühringer
  2. Ulrich Hohmann
  3. Laura Fin
  4. Belén Pacheco-Fiallos
  5. Ulla Schellhaas
  6. Julius Brennecke
  7. Clemens Plaschka
(2020)
Structure of the human core transcription-export complex reveals a hub for multivalent interactions
eLife 9:e61503.
https://doi.org/10.7554/eLife.61503

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