Structure of the human core transcription-export complex reveals a hub for multivalent interactions
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 mar...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/61503 |
| _version_ | 1818028517198135296 |
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| author | Thomas Pühringer Ulrich Hohmann Laura Fin Belén Pacheco-Fiallos Ulla Schellhaas Julius Brennecke Clemens Plaschka |
| author_facet | Thomas Pühringer Ulrich Hohmann Laura Fin Belén Pacheco-Fiallos Ulla Schellhaas Julius Brennecke Clemens Plaschka |
| author_sort | Thomas Pühringer |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T05:05:03Z |
| format | Article |
| id | doaj.art-68e3dd13e4cd4c2cb84911aa21daf67f |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T05:05:03Z |
| publishDate | 2020-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-68e3dd13e4cd4c2cb84911aa21daf67f2022-12-22T02:01:16ZengeLife Sciences Publications LtdeLife2050-084X2020-11-01910.7554/eLife.61503Structure of the human core transcription-export complex reveals a hub for multivalent interactionsThomas Pühringer0https://orcid.org/0000-0001-9127-9120Ulrich Hohmann1https://orcid.org/0000-0003-2124-1439Laura Fin2Belén Pacheco-Fiallos3Ulla Schellhaas4https://orcid.org/0000-0002-9684-9839Julius Brennecke5Clemens Plaschka6https://orcid.org/0000-0002-6020-9514Research Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, AustriaResearch Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, Austria; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, AustriaResearch Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, AustriaResearch Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, AustriaResearch Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, AustriaInstitute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, AustriaResearch Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), Vienna, AustriaThe 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.https://elifesciences.org/articles/61503mRNA packagingmRNA exportcryo-EMmacromolecular complexes |
| spellingShingle | Thomas Pühringer Ulrich Hohmann Laura Fin Belén Pacheco-Fiallos Ulla Schellhaas Julius Brennecke Clemens Plaschka Structure of the human core transcription-export complex reveals a hub for multivalent interactions eLife mRNA packaging mRNA export cryo-EM macromolecular complexes |
| title | Structure of the human core transcription-export complex reveals a hub for multivalent interactions |
| title_full | Structure of the human core transcription-export complex reveals a hub for multivalent interactions |
| title_fullStr | Structure of the human core transcription-export complex reveals a hub for multivalent interactions |
| title_full_unstemmed | Structure of the human core transcription-export complex reveals a hub for multivalent interactions |
| title_short | Structure of the human core transcription-export complex reveals a hub for multivalent interactions |
| title_sort | structure of the human core transcription export complex reveals a hub for multivalent interactions |
| topic | mRNA packaging mRNA export cryo-EM macromolecular complexes |
| url | https://elifesciences.org/articles/61503 |
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