Cargando…
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...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744094/ https://www.ncbi.nlm.nih.gov/pubmed/33191911 http://dx.doi.org/10.7554/eLife.61503 |
_version_ | 1783624367487320064 |
---|---|
author | Pühringer, Thomas Hohmann, Ulrich Fin, Laura Pacheco-Fiallos, Belén Schellhaas, Ulla Brennecke, Julius Plaschka, Clemens |
author_facet | Pühringer, Thomas Hohmann, Ulrich Fin, Laura Pacheco-Fiallos, Belén Schellhaas, Ulla Brennecke, Julius Plaschka, Clemens |
author_sort | Pühringer, Thomas |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-7744094 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-77440942020-12-21 Structure of the human core transcription-export complex reveals a hub for multivalent interactions Pühringer, Thomas Hohmann, Ulrich Fin, Laura Pacheco-Fiallos, Belén Schellhaas, Ulla Brennecke, Julius Plaschka, Clemens eLife Chromosomes and Gene Expression 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. eLife Sciences Publications, Ltd 2020-11-16 /pmc/articles/PMC7744094/ /pubmed/33191911 http://dx.doi.org/10.7554/eLife.61503 Text en © 2020, Pühringer et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Chromosomes and Gene Expression Pühringer, Thomas Hohmann, Ulrich Fin, Laura Pacheco-Fiallos, Belén Schellhaas, Ulla Brennecke, Julius Plaschka, Clemens Structure of the human core transcription-export complex reveals a hub for multivalent interactions |
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 | Chromosomes and Gene Expression |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744094/ https://www.ncbi.nlm.nih.gov/pubmed/33191911 http://dx.doi.org/10.7554/eLife.61503 |
work_keys_str_mv | AT puhringerthomas structureofthehumancoretranscriptionexportcomplexrevealsahubformultivalentinteractions AT hohmannulrich structureofthehumancoretranscriptionexportcomplexrevealsahubformultivalentinteractions AT finlaura structureofthehumancoretranscriptionexportcomplexrevealsahubformultivalentinteractions AT pachecofiallosbelen structureofthehumancoretranscriptionexportcomplexrevealsahubformultivalentinteractions AT schellhaasulla structureofthehumancoretranscriptionexportcomplexrevealsahubformultivalentinteractions AT brenneckejulius structureofthehumancoretranscriptionexportcomplexrevealsahubformultivalentinteractions AT plaschkaclemens structureofthehumancoretranscriptionexportcomplexrevealsahubformultivalentinteractions |