title: The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression.
abstract: Nuclear pore complexes (NPCs) influence gene expression besides their established function in nuclear transport. The TREX-2 complex localizes to the NPC basket and affects gene-NPC interactions, transcription, and mRNA export. How TREX-2 regulates the gene expression machinery is unknown. Here, we show that TREX-2 interacts with the Mediator complex, an essential regulator of RNA Polymerase (Pol) II. Structural and biochemical studies identify a conserved region on TREX-2, which directly binds the Mediator Med31/Med7N submodule. TREX-2 regulates assembly of Mediator with the Cdk8 kinase and is required for recruitment and site-specific phosphorylation of Pol II. Transcriptome and phenotypic profiling confirm that TREX-2 and Med31 are functionally interdependent at specific genes. TREX-2 additionally uses its Mediator-interacting surface to regulate mRNA export suggesting a mechanism for coupling transcription initiation and early steps of mRNA processing. Our data provide mechanistic insight into how an NPC-associated adaptor complex accesses the core transcription machinery.
authors: Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter Campus (VBC), Dr. Bohr-Gasse 9/3, 1030 Vienna, Austria.
authors: Maren
authors: M
authors: Schneider
authors: Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, 1030 Vienna, Austria.
authors: Doris
authors: D
authors: Hellerschmied
authors: Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter Campus (VBC), Dr. Bohr-Gasse 9/3, 1030 Vienna, Austria.
authors: Tobias
authors: T
authors: Schubert
authors: Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter Campus (VBC), Dr. Bohr-Gasse 9/3, 1030 Vienna, Austria.
authors: Stefan
authors: S
authors: Amlacher
authors: Department of Biochemistry and Molecular Biology, Center for Eukaryotic Gene Regulation, Pennsylvania State University, University Park, PA 16802, USA.
authors: Vinesh
authors: V
authors: Vinayachandran
authors: Department of Biochemistry and Molecular Biology, Center for Eukaryotic Gene Regulation, Pennsylvania State University, University Park, PA 16802, USA.
authors: Rohit
authors: R
authors: Reja
authors: Department of Biochemistry and Molecular Biology, Center for Eukaryotic Gene Regulation, Pennsylvania State University, University Park, PA 16802, USA.
authors: B Franklin
authors: BF
authors: Pugh
authors: Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, 1030 Vienna, Austria.
authors: Tim
authors: T
authors: Clausen
authors: Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter Campus (VBC), Dr. Bohr-Gasse 9/3, 1030 Vienna, Austria. Electronic address: alwin.koehler@mfpl.ac.at.
authors: Alwin
authors: A
authors: Köhler
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D056892:Mediator Complex / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism*; D022022:Nuclear Pore / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018272:Porins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D012261:Ribonucleoproteins / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D014158:Transcription, Genetic; D059467:Transcriptome; D014961:X-Ray Diffraction
chemical_list: D056892:Mediator Complex; D046912:Multiprotein Complexes; D029543:Nucleocytoplasmic Transport Proteins; D018272:Porins; D012261:Ribonucleoproteins; C103382:SAC3 protein, S cerevisiae; C117424:SEM1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C476348:Thp1 protein, S cerevisiae; D012319:RNA Polymerase II; D046988:Proteasome Endopeptidase Complex