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, Benjamin Franklin Pugh, Tim Clausen, Alwin Köhler

Research output: Contribution to journalArticle

51 Citations (Scopus)

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

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Mediator Complex
Nuclear Pore
Transcription
Gene expression
Gene Expression
Messenger RNA
Machinery
Genes
Phosphorylation
RNA Polymerase II
Cell Nucleus Active Transport
Gene Expression Profiling
Phosphotransferases
Processing

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Schneider, M., Hellerschmied, D., Schubert, T., Amlacher, S., Vinayachandran, V., Reja, R., ... 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
Schneider, Maren ; Hellerschmied, Doris ; Schubert, Tobias ; Amlacher, Stefan ; Vinayachandran, Vinesh ; Reja, Rohit ; Pugh, Benjamin Franklin ; Clausen, Tim ; Köhler, Alwin. / The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression. In: Cell. 2015 ; Vol. 162, No. 5. pp. 1016-1028.
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Schneider, M, Hellerschmied, D, Schubert, T, Amlacher, S, Vinayachandran, V, Reja, R, Pugh, BF, Clausen, T & Köhler, A 2015, 'The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression', Cell, vol. 162, no. 5, pp. 1016-1028. https://doi.org/10.1016/j.cell.2015.07.059

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, Benjamin Franklin; Clausen, Tim; Köhler, Alwin.

In: Cell, Vol. 162, No. 5, 27.08.2015, p. 1016-1028.

Research output: Contribution to journalArticle

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AU - Schneider, Maren

AU - Hellerschmied, Doris

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AU - Vinayachandran, Vinesh

AU - Reja, Rohit

AU - Pugh, Benjamin Franklin

AU - Clausen, Tim

AU - Köhler, Alwin

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N2 - 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.

AB - 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.

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Schneider M, Hellerschmied D, Schubert T, Amlacher S, Vinayachandran V, Reja R et al. The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression. Cell. 2015 Aug 27;162(5):1016-1028. https://doi.org/10.1016/j.cell.2015.07.059