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TitleStructure of the human core transcription-export complex reveals a hub for multivalent interactions.
Journal, issue, pagesElife, Vol. 9, Year 2020
Publish dateNov 16, 2020
AuthorsThomas Pühringer / Ulrich Hohmann / Laura Fin / Belén Pacheco-Fiallos / Ulla Schellhaas / Julius Brennecke / Clemens Plaschka /
PubMed AbstractThe 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.
External linksElife / PubMed:33191911 / PubMed Central
MethodsEM (single particle)
Resolution3.3 - 4.7 Å
Structure data

EMDB-11853:
Structure of the human THO - UAP56 complex (Map A)
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-11854:
Structure of the human THO - UAP56 complex (Map C)
Method: EM (single particle) / Resolution: 4.7 Å

EMDB-11855:
Structure of the human THO - UAP56 complex (Map D)
Method: EM (single particle) / Resolution: 4.6 Å

EMDB-11856:
Structure of the human THO - UAP56 complex (Map E)
Method: EM (single particle) / Resolution: 4.7 Å

11857

7apk

EMDB-11857: Structure of the human THO - UAP56 complex (Map B)
PDB-7apk: Structure of the human THO - UAP56 complex
Method: EM (single particle) / Resolution: 3.3 Å

Source
  • homo sapiens (human)
KeywordsGENE REGULATION / mRNA / nucleocytoplasmic transport / R-loop / gene expression

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