A Genetic Interaction Map of RNA-Processing Factors Reveals Links between Sem1/Dss1-Containing Complexes and mRNA Export and Splicing

Gwendolyn M. Wilmes, Megan Bergkessel, Sourav Bandyopadhyay, Michael Shales, Hannes Braberg, Gerard Cagney, Sean R. Collins, Gregg B. Whitworth, Tracy L. Kress, Jonathan S. Weissman, Trey Ideker, Christine Guthrie (Lead / Corresponding author), Nevan J. Krogan (Lead / Corresponding author)

Research output: Contribution to journalArticle

182 Citations (Scopus)

Abstract

We used a quantitative, high-density genetic interaction map, or E-MAP (Epistatic MiniArray Profile), to interrogate the relationships within and between RNA-processing pathways. Due to their complexity and the essential roles of many of the components, these pathways have been difficult to functionally dissect. Here, we report the results for 107,155 individual interactions involving 552 mutations, 166 of which are hypomorphic alleles of essential genes. Our data enabled the discovery of links between components of the mRNA export and splicing machineries and Sem1/Dss1, a component of the 19S proteasome. In particular, we demonstrate that Sem1 has a proteasome-independent role in mRNA export as a functional component of the Sac3-Thp1 complex. Sem1 also interacts with Csn12, a component of the COP9 signalosome. Finally, we show that Csn12 plays a role in pre-mRNA splicing, which is independent of other signalosome components. Thus, Sem1 is involved in three separate and functionally distinct complexes.

Original languageEnglish
Pages (from-to)735-746
Number of pages12
JournalMolecular Cell
Volume32
Issue number5
Early online date4 Dec 2008
DOIs
Publication statusPublished - 5 Dec 2008

Keywords

  • PROTEINS
  • RNA
  • SYSBIO

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    Wilmes, G. M., Bergkessel, M., Bandyopadhyay, S., Shales, M., Braberg, H., Cagney, G., Collins, S. R., Whitworth, G. B., Kress, T. L., Weissman, J. S., Ideker, T., Guthrie, C., & Krogan, N. J. (2008). A Genetic Interaction Map of RNA-Processing Factors Reveals Links between Sem1/Dss1-Containing Complexes and mRNA Export and Splicing. Molecular Cell, 32(5), 735-746. https://doi.org/10.1016/j.molcel.2008.11.012