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

  • Elife. 2020 Nov 16:9:e61503. doi: 10.7554/eLife.61503.
Thomas Pühringer  #  1 ,  Ulrich Hohmann  #  1  2 ,  Laura Fin  1 ,  Belén Pacheco-Fiallos  1 ,  Ulla Schellhaas  1 ,  Julius Brennecke  2 ,  Clemens Plaschka  1
Affiliations
  • 1. Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria.
  • 2. Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria.
  • # Contributed equally.
PMID: 33191911 DOI: 10.7554/eLife.61503
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.

Keywords
chromosomes; cryo-EM; gene expression; human; mRNA export; mRNA packaging; macromolecular complexes; molecular biophysics; structural biology.