Structure of the human core transcription-export complex reveals a hub for multivalent interactions
- Research Institute of Molecular Pathology (IMP), Austria
- Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Austria
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 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.
Data availability
Three-dimensional cryo-EM density maps A, B, C, D, and E have been deposited in the Electron Microscopy Data Bank under the accession numbers EMD-11853, EMD-11857, EMD-11854, EMD-11855, EMD-11856, respectively. The coordinate file of the human THO-UAP56 complex has been deposited in the Protein Data Bank under the accession number 7APK.
-
Three-dimensional cryo-EM density map AElectron Microscopy Data Bank, EMD-11853.
-
Three-dimensional cryo-EM density map BElectron Microscopy Data Bank, EMD-11857.
-
Three-dimensional cryo-EM density map CElectron Microscopy Data Bank, EMD-11854.
-
Three-dimensional cryo-EM density maps DElectron Microscopy Data Bank, EMD-11855.
-
Three-dimensional cryo-EM density maps EElectron Microscopy Data Bank, EMD-11856.
Article and author information
Author details
Funding
Boehringer Ingelheim
- Clemens Plaschka
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (P2GEP3_188343)
- Ulrich Hohmann
H2020 European Research Council (ERC-2015-CoG 682181)
- Julius Brennecke
Austrian Science Fund (F4303 and W1207)
- Julius Brennecke
Österreichischen Akademie der Wissenschaften
- Julius Brennecke
H2020 European Research Council (ERC-2020-STG 949081)
- Clemens Plaschka
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Karsten Weis, ETH Zurich, Switzerland
Version history
- Received: July 28, 2020
- Accepted: November 13, 2020
- Accepted Manuscript published: November 16, 2020 (version 1)
- Version of Record published: December 16, 2020 (version 2)
Copyright
© 2020, Pühringer et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 7,077
- views
-
- 951
- downloads
-
- 45
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Structure of the human core transcription-export complex reveals a hub for multivalent interactions
eLife 9:e61503.
https://doi.org/10.7554/eLife.61503
Further reading
-
- Chromosomes and Gene Expression
- Immunology and Inflammation
Ikaros is a transcriptional factor required for conventional T cell development, differentiation, and anergy. While the related factors Helios and Eos have defined roles in regulatory T cells (Treg), a role for Ikaros has not been established. To determine the function of Ikaros in the Treg lineage, we generated mice with Treg-specific deletion of the Ikaros gene (Ikzf1). We find that Ikaros cooperates with Foxp3 to establish a major portion of the Treg epigenome and transcriptome. Ikaros-deficient Treg exhibit Th1-like gene expression with abnormal production of IL-2, IFNg, TNFa, and factors involved in Wnt and Notch signaling. While Ikzf1-Treg-cko mice do not develop spontaneous autoimmunity, Ikaros-deficient Treg are unable to control conventional T cell-mediated immune pathology in response to TCR and inflammatory stimuli in models of IBD and organ transplantation. These studies establish Ikaros as a core factor required in Treg for tolerance and the control of inflammatory immune responses.
-
- Cell Biology
- Chromosomes and Gene Expression
Heat stress is a major threat to global crop production, and understanding its impact on plant fertility is crucial for developing climate-resilient crops. Despite the known negative effects of heat stress on plant reproduction, the underlying molecular mechanisms remain poorly understood. Here, we investigated the impact of elevated temperature on centromere structure and chromosome segregation during meiosis in Arabidopsis thaliana. Consistent with previous studies, heat stress leads to a decline in fertility and micronuclei formation in pollen mother cells. Our results reveal that elevated temperature causes a decrease in the amount of centromeric histone and the kinetochore protein BMF1 at meiotic centromeres with increasing temperature. Furthermore, we show that heat stress increases the duration of meiotic divisions and prolongs the activity of the spindle assembly checkpoint during meiosis I, indicating an impaired efficiency of the kinetochore attachments to spindle microtubules. Our analysis of mutants with reduced levels of centromeric histone suggests that weakened centromeres sensitize plants to elevated temperature, resulting in meiotic defects and reduced fertility even at moderate temperatures. These results indicate that the structure and functionality of meiotic centromeres in Arabidopsis are highly sensitive to heat stress, and suggest that centromeres and kinetochores may represent a critical bottleneck in plant adaptation to increasing temperatures.
