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

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54 Scopus citations

Abstract

Summary 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.

Original languageEnglish (US)
Pages (from-to)1016-1028
Number of pages13
JournalCell
Volume162
Issue number5
DOIs
StatePublished - Aug 27 2015

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Schneider, M., Hellerschmied, D., Schubert, T., Amlacher, S., Vinayachandran, V., Reja, R., Pugh, B. F., Clausen, T., & Köhler, A. (2015). The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression. Cell, 162(5), 1016-1028. https://doi.org/10.1016/j.cell.2015.07.059