Structural insights into the nucleic acid remodeling mechanisms of the yeast THO-Sub2 complex
- Max Planck Institute of Biochemistry, Germany
Abstract
The yeast THO complex is recruited to active genes and interacts with the RNA-dependent ATPase Sub2 to facilitate the formation of mature export-competent mRNPs and to prevent the co-transcriptional formation of RNA:DNA-hybrid-containing structures. How THO-containing complexes function at the mechanistic level is unclear. Here, we elucidated a 3.4Å resolution structure of S. cerevisiae THO-Sub2 by cryo-electron microscopy. THO subunits Tho2 and Hpr1 intertwine to form a platform that is bound by Mft1, Thp2, and Tex1. The resulting complex homodimerizes in an asymmetric fashion, with a Sub2 molecule attached to each protomer. The homodimerization interfaces serve as a fulcrum for a seesaw-like movement concomitant with conformational changes of the Sub2 ATPase. The overall structural architecture and topology suggest the molecular mechanisms of nucleic acid remodeling during mRNA biogenesis.
Data availability
Cryo-EM maps are available in the Electron Microscopy Data Bank (11859 and 11871). Atomic models are available in the Protein Data Bank (7APX and 7AQO).
Article and author information
Author details
Funding
European Commission (EXORICO)
- Elena Conti
Deutsche Forschungsgemeinschaft (201302640)
- Elena Conti
Deutsche Forschungsgemeinschaft (369799452)
- 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
- Karsten Weis, ETH Zurich, Switzerland
Version history
- Received: July 27, 2020
- Accepted: November 13, 2020
- Accepted Manuscript published: November 16, 2020 (version 1)
- Version of Record published: December 16, 2020 (version 2)
- Version of Record updated: November 15, 2023 (version 3)
Copyright
© 2020, Schuller 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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Structural insights into the nucleic acid remodeling mechanisms of the yeast THO-Sub2 complex
eLife 9:e61467.
https://doi.org/10.7554/eLife.61467
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