Journal: Elife / Year: 2020 Title: Structure of the human core transcription-export complex reveals a hub for multivalent interactions. Authors: Thomas Pühringer / Ulrich Hohmann / Laura Fin / Belén Pacheco-Fiallos / Ulla Schellhaas / Julius Brennecke / Clemens Plaschka / 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 ...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.
History
Deposition
Oct 17, 2020
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Header (metadata) release
Dec 16, 2020
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Map release
Dec 16, 2020
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Update
May 1, 2024
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Current status
May 1, 2024
Processing site: PDBe / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron optics
Illumination mode: OTHER / Imaging mode: OTHER
Image recording
Film or detector model: GATAN K3 (6k x 4k) / Number grids imaged: 2 / Number real images: 26303 / Average exposure time: 3.8 sec. / Average electron dose: 50.0 e/Å2
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
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Image processing
Particle selection
Number selected: 1570265
Startup model
Type of model: INSILICO MODEL
Initial angle assignment
Type: MAXIMUM LIKELIHOOD
Final angle assignment
Type: MAXIMUM LIKELIHOOD
Final reconstruction
Resolution.type: BY AUTHOR / Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 195098
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Atomic model buiding 1
Refinement
Space: REAL / Protocol: AB INITIO MODEL
Output model
PDB-7apk: Structure of the human THO - UAP56 complex
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