A genetic interaction map of RNA-processing factors reveals links between Sem1/Dss1-containing complexes and mRNA export and splicing.
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.
Wilmes
Gwendolyn M
GM
Department of Biochemistry and Biophysics, University of California, San Francisco, 600 16th Street, Genentech Hall, San Francisco, CA 94143-2200, USA.
Bergkessel
Megan
M
Bandyopadhyay
Sourav
S
Shales
Michael
M
Braberg
Hannes
H
Cagney
Gerard
G
Collins
Sean R
SR
Whitworth
Gregg B
GB
Kress
Tracy L
TL
Weissman
Jonathan S
JS
Ideker
Trey
T
Guthrie
Christine
C
Krogan
Nevan J
NJ
D000075686:COP9 Signalosome Complex; D005095:Exoribonucleases; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D025941:Protein Interaction Mapping; D012323:RNA Processing, Post-Transcriptional; D012326:RNA Splicing; D034443:RNA Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
D046912:Multiprotein Complexes; D012333:RNA, Messenger; C117424:SEM1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D005095:Exoribonucleases; C098317:DSS1 protein, S cerevisiae; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex; D046988:Proteasome Endopeptidase Complex