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Structural basis for binding the TREX2 complex to nuclear pores, GAL1 localisation and mRNA export

DOI: 10.1093/nar/gku252 DOI Help
PMID: 24705649 PMID Help

Authors: Divyang Jani (MRC Laboratory of Molecular Biology, Cambridge, U.K.) , Eugene Valkov (MRC Laboratory of Molecular Biology, Cambridge, U.K.) , M. Stewart (MRC Laboratory of Molecular Biology, Cambridge, U.K.)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nucleic Acids Research , VOL 42 (10) , PAGES 6686 - 6697

State: Published (Approved)
Published: June 2014
Diamond Proposal Number(s): 8547

Open Access Open Access

Abstract: The conserved Sac3:Thp1:Sem1:Sus1:Cdc31 (TREX2) complex binds to nuclear pore complexes (NPCs) and, in addition to integrating mRNA nuclear export with preceding steps in the gene expression pathway, facilitates re-positioning of highly regulated actively transcribing genes (such as GAL1) to NPCs. Although TREX2 is thought to bind NPC protein Nup1, defining the precise role of this interaction has been frustrated by the complex pleiotropic phenotype exhibited by nup1Δ strains. To provide a structural framework for understanding the binding of TREX2 to NPCs and its function in the gene expression pathway, we have determined the structure of the Nup1:TREX2 interaction interface and used this information to engineer a Sac3 variant that impairs NPC binding while not compromising TREX2 assembly. This variant inhibited the NPC association of both de-repressed and activated GAL1 and also produced mRNA export and growth defects. These results indicate that the TREX2:Nup1 interaction facilitates the efficient nuclear export of bulk mRNA together with the re-positioning of GAL1 to NPCs that is required for transcriptional control that is mediated by removal of SUMO from repressors by NPC-bound Ulp1

Journal Keywords: Cell; Cell; Galactokinase ; Models ; Molecular ; Mutation ; Nuclear; Nuclear; Nuclear; Nucleocytoplasmic; Porins ; Protein; RNA; RNA ; Messenger ; RNA-Binding; Saccharomyces; Saccharomyces cerevisiae Proteins

Subject Areas: Biology and Bio-materials


Instruments: I04-Macromolecular Crystallography

Other Facilities: No

Added On: 25/09/2014 10:01

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