The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression

Maren Schneider; Doris Hellerschmied; Tobias Schubert; Stefan Amlacher; Vinesh Vinayachandran; Rohit Reja; B Franklin Pugh; Tim Clausen; Alwin Köhler

doi:10.1016/j.cell.2015.07.059

The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression

Cell. 2015 Aug 27;162(5):1016-28. doi: 10.1016/j.cell.2015.07.059.

Authors

Maren Schneider¹, Doris Hellerschmied², Tobias Schubert¹, Stefan Amlacher¹, Vinesh Vinayachandran³, Rohit Reja³, B Franklin Pugh³, Tim Clausen², Alwin Köhler⁴

Affiliations

¹ Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter Campus (VBC), Dr. Bohr-Gasse 9/3, 1030 Vienna, Austria.
² Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, 1030 Vienna, Austria.
³ Department of Biochemistry and Molecular Biology, Center for Eukaryotic Gene Regulation, Pennsylvania State University, University Park, PA 16802, USA.
⁴ 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.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Humans
Mediator Complex / metabolism*
Models, Molecular
Molecular Sequence Data
Multiprotein Complexes / chemistry
Multiprotein Complexes / metabolism*
Nuclear Pore / metabolism
Nucleocytoplasmic Transport Proteins / chemistry*
Nucleocytoplasmic Transport Proteins / genetics
Nucleocytoplasmic Transport Proteins / metabolism*
Porins / chemistry*
Porins / genetics
Porins / metabolism*
Promoter Regions, Genetic
Proteasome Endopeptidase Complex / chemistry
Proteasome Endopeptidase Complex / metabolism
RNA Polymerase II / metabolism
Ribonucleoproteins / chemistry
Ribonucleoproteins / metabolism
Saccharomyces cerevisiae / chemistry
Saccharomyces cerevisiae / metabolism*
Saccharomyces cerevisiae Proteins / chemistry*
Saccharomyces cerevisiae Proteins / genetics
Saccharomyces cerevisiae Proteins / metabolism*
Sequence Alignment
Transcription, Genetic*
Transcriptome
X-Ray Diffraction

Substances

Mediator Complex
Multiprotein Complexes
Nucleocytoplasmic Transport Proteins
Porins
Ribonucleoproteins
SAC3 protein, S cerevisiae
SEM1 protein, S cerevisiae
Saccharomyces cerevisiae Proteins
Thp1 protein, S cerevisiae
RNA Polymerase II
Proteasome Endopeptidase Complex

Associated data

PDB/4TRQ

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding