Journal
CELL
Volume 162, Issue 5, Pages 1016-1028Publisher
CELL PRESS
DOI: 10.1016/j.cell.2015.07.059
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Funding
- ERC [281354]
- Austrian Science Fund (FWF) [Y557-B11]
- Boehringer Ingelheim
- NIH [GM059055]
- Austrian Science Fund (FWF) [Y 557] Funding Source: researchfish
- European Research Council (ERC) [281354] Funding Source: European Research Council (ERC)
- Austrian Science Fund (FWF) [Y557] Funding Source: Austrian Science Fund (FWF)
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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.
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