TY - JOUR
T1 - A Genetic Interaction Map of RNA-Processing Factors Reveals Links between Sem1/Dss1-Containing Complexes and mRNA Export and Splicing
AU - Wilmes, Gwendolyn M.
AU - Bergkessel, Megan
AU - Bandyopadhyay, Sourav
AU - Shales, Michael
AU - Braberg, Hannes
AU - Cagney, Gerard
AU - Collins, Sean R.
AU - Whitworth, Gregg B.
AU - Kress, Tracy L.
AU - Weissman, Jonathan S.
AU - Ideker, Trey
AU - Guthrie, Christine
AU - Krogan, Nevan J.
N1 - Funding Information:
We would like to thank H. Kobayashi, T. Kodadek, D. Kellogg, and C. Dargement for antibodies; D. Cameron for strains; A. Chan, E. Cheng, L. Jieying, M. Dinglasin, and C. Wong for technical assistance; M. Schuldiner for help with the screens; P. Kemmerman for help with the website; L. Booth for work on ynr004wΔ; and V. Panse for sharing unpublished data. We would like to thank members of the Guthrie lab, A. Frankel and J. Gross, for reading and advice on the manuscript. G.M.W. was supported by postdoctoral fellowships from the American Cancer Society and the Sandler Foundation. M.B. was supported by an HHMI predoctoral fellowship. C.G. is an American Cancer Society Research Professor of Molecular Genetics. This research was funded by NIH grant GM21119 (C.G.) and from Sandler Family Funding (N.J.K.).
PY - 2008/12/5
Y1 - 2008/12/5
N2 - 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.
AB - 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.
KW - PROTEINS
KW - RNA
KW - SYSBIO
UR - https://www.scopus.com/pages/publications/56849094282
U2 - 10.1016/j.molcel.2008.11.012
DO - 10.1016/j.molcel.2008.11.012
M3 - Article
C2 - 19061648
AN - SCOPUS:56849094282
SN - 1097-2765
VL - 32
SP - 735
EP - 746
JO - Molecular Cell
JF - Molecular Cell
IS - 5
ER -