Structural insights into the nucleic acid remodeling mechanisms of the yeast THO-Sub2 complex

• Main Authors: Sandra K Schuller, Jan M Schuller, J Rajan Prabu, Marc Baumgärtner, Fabien Bonneau, Jérôme Basquin, Elena Conti
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2020-11-01
• Series: eLife
• Subjects: RNA; helicase; R-loops; CryoEM; RNA export; transcription
• Online Access: https://elifesciences.org/articles/61467

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 messenger ribonucleoprotein particles 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 3.4 Å resolution structure of Saccharomyces 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.