The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression
Maren Schneider 4, Doris Hellerschmied 4, Tobias Schubert 4, Stefan Amlacher, Vinesh Vinayachandran, Rohit Reja, B. Franklin Pugh, Tim Clausen, Alwin Köhler
•The nuclear pore-associated TREX-2 complex directly interacts with Mediator
•TREX-2 regulates Mediator association with Cdk8 and RNA Pol II Ser5 phosphorylation
•TREX-2 and the Med31 submodule co-regulate specific inducible and constitutive genes
•A similar TREX-2 surface promotes both transcription and mRNA export
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.
Received: June 18, 2014; Received in revised form: May 5, 2015; Accepted: July 6, 2015;
© 2015 Elsevier Inc. Published by Elsevier Inc.
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