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 Collins, Gregg B. Whitworth, Tracy L. Kress, Jonathan S. Weissman, Trey Ideker, Christine Guthrie, Nevan J. Krogan

Research output: Contribution to journalArticle

180 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 (US)
Pages (from-to)735-746
Number of pages12
JournalMolecular Cell
Volume32
Issue number5
DOIs
StatePublished - Dec 5 2008
Externally publishedYes

Fingerprint

Proteasome Endopeptidase Complex
RNA
Messenger RNA
Essential Genes
RNA Precursors
Alleles
Mutation
COP9 signalosome complex

Keywords

  • PROTEINS
  • RNA
  • SYSBIO

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Wilmes, G. M., Bergkessel, M., Bandyopadhyay, S., Shales, M., Braberg, H., Cagney, G., ... 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

A Genetic Interaction Map of RNA-Processing Factors Reveals Links between Sem1/Dss1-Containing Complexes and mRNA Export and Splicing. / Wilmes, Gwendolyn M.; Bergkessel, Megan; Bandyopadhyay, Sourav; Shales, Michael; Braberg, Hannes; Cagney, Gerard; Collins, Sean; Whitworth, Gregg B.; Kress, Tracy L.; Weissman, Jonathan S.; Ideker, Trey; Guthrie, Christine; Krogan, Nevan J.

In: Molecular Cell, Vol. 32, No. 5, 05.12.2008, p. 735-746.

Research output: Contribution to journalArticle

Wilmes, GM, Bergkessel, M, Bandyopadhyay, S, Shales, M, Braberg, H, Cagney, G, Collins, S, Whitworth, GB, Kress, TL, Weissman, JS, Ideker, T, Guthrie, C & Krogan, NJ 2008, 'A Genetic Interaction Map of RNA-Processing Factors Reveals Links between Sem1/Dss1-Containing Complexes and mRNA Export and Splicing', Molecular Cell, vol. 32, no. 5, pp. 735-746. https://doi.org/10.1016/j.molcel.2008.11.012
Wilmes, Gwendolyn M. ; Bergkessel, Megan ; Bandyopadhyay, Sourav ; Shales, Michael ; Braberg, Hannes ; Cagney, Gerard ; Collins, Sean ; Whitworth, Gregg B. ; Kress, Tracy L. ; Weissman, Jonathan S. ; Ideker, Trey ; Guthrie, Christine ; Krogan, Nevan J. / A Genetic Interaction Map of RNA-Processing Factors Reveals Links between Sem1/Dss1-Containing Complexes and mRNA Export and Splicing. In: Molecular Cell. 2008 ; Vol. 32, No. 5. pp. 735-746.
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