Distinct and evolutionary conserved structural features of the human nuclear exosome complex
- Max Planck Institute of Biochemistry, Germany
Abstract
The nuclear RNA exosome complex mediates the processing of structured RNAs and the decay of aberrant non-coding RNAs, an important function particularly in human cells. Most mechanistic studies to date have focused on the yeast system. Here, we reconstituted and studied the properties of a recombinant 14-subunit human nuclear exosome complex. In biochemical assays, the human exosome embeds a longer RNA channel than its yeast counterpart. The 3.8 Å resolution cryo-EM structure of the core complex bound to a single-stranded RNA reveals that the RNA channel path is formed by two distinct features of the hDIS3 exoribonuclease: an open conformation and a domain organization more similar to bacterial RNase II than to yeast Rrp44. The cryo-EM structure of the holo-complex shows how obligate nuclear cofactors position the hMTR4 helicase at the entrance of the core complex, suggesting a striking structural conservation from lower to higher eukaryotes.
Data availability
The cryo-EM density maps are deposited in the Electron Microscopy Data Bank under accession numbers EMD-0127 and EMD-0128. The atomic model is deposited in the Protein Data Bank (PDB) under accession number 6H25.
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Human nuclear RNA exosome EXO-14 complex (cryo-EM density map)Publicly available at the Electron Microscopy Data Bank (accession no: EMD-0127).
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Cryo-EM density mapPublicly available at the Electron Microscopy Data Bank (accession no: EMD-0128).
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Human nuclear RNA exosome EXO-10-MPP6 complex (atomic model)Publicly available at the RCSB Protein Data Bank (accession no: 6H25).
Article and author information
Author details
Funding
European Molecular Biology Organization (ALTF 1008-2015)
- Piotr Gerlach
European Commission (ERC-2016-ADG 740329 EXORICO)
- Elena Conti
Deutsche Forschungsgemeinschaft (SFB646)
- Elena Conti
Louis-Jeantet Foundation
- Elena Conti
Max-Planck-Gesellschaft
- Elena Conti
Deutsche Forschungsgemeinschaft (SFB1035)
- Elena Conti
Deutsche Forschungsgemeinschaft (GRK1721)
- Elena Conti
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Sjors HW Scheres, MRC Laboratory of Molecular Biology, United Kingdom
Publication history
- Received: May 26, 2018
- Accepted: July 17, 2018
- Accepted Manuscript published: July 26, 2018 (version 1)
- Version of Record published: August 2, 2018 (version 2)
Copyright
© 2018, Gerlach 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.
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Distinct and evolutionary conserved structural features of the human nuclear exosome complex
eLife 7:e38686.
https://doi.org/10.7554/eLife.38686
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