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

© 2020, Pühringer et al..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:9

Enthalten in:

eLife - 9(2020) vom: 16. Nov.

Sprache:

Englisch

Beteiligte Personen:

Pühringer, Thomas [VerfasserIn]
Hohmann, Ulrich [VerfasserIn]
Fin, Laura [VerfasserIn]
Pacheco-Fiallos, Belén [VerfasserIn]
Schellhaas, Ulla [VerfasserIn]
Brennecke, Julius [VerfasserIn]
Plaschka, Clemens [VerfasserIn]

Links:

Volltext

Themen:

Chromosomes
Cryo-EM
Gene expression
Human
Journal Article
MRNA export
MRNA packaging
Macromolecular complexes
Molecular biophysics
Multiprotein Complexes
RNA, Messenger
RNA-Binding Proteins
Research Support, Non-U.S. Gov't
Structural biology

Anmerkungen:

Date Completed 31.03.2021

Date Revised 31.03.2021

published: Electronic

Citation Status MEDLINE

doi:

10.7554/eLife.61503

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM317593072