Format

Send to

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

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

Author information

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.

PMID:
26317468
PMCID:
PMC4644235
DOI:
10.1016/j.cell.2015.07.059
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center