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The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression
- Schneider, Maren, Hellerschmied, Doris, Schubert, Tobias, Amlacher, Stefan, Vinayachandran, Vinesh, Reja, Rohit, Pugh, B. Franklin, Clausen, Tim, Köhler, Alwin
- Cell 2015 v.162 pp. 1016-1028
- DNA-directed RNA polymerase, RNA transport, gene expression, genes, messenger RNA, nucleoporins, phenotype, phosphorylation, transcriptome
- 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.