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The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression.

Schneider M, Hellerschmied D, Schubert T, Amlacher S, Vinayachandran V, Reja R, Pugh BF, Clausen T, Köhler A - Cell (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter Campus (VBC), Dr. Bohr-Gasse 9/3, 1030 Vienna, Austria.

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The Sac3 PCI Domain Promotes Transcription and mRNA ExportMechanism for a relay between TREX-2, Mediator, and Pol II. Model depicts the putative overall topology of TREX-2 and its interaction with Mediator. (1) Docking to Mediator involves the conserved pair of Sac3 R256/R288 residues (red sticks) and the Med31 submodule (magenta). (2) TREX-2 regulates Cdk8 kinase module association. (3) TREX-2, Cdk8, and Med31 impact on RNA Pol II CTD Ser5 phosphorylation (S5; yellow). (4) TREX-2 also influences mRNA export via the PCI surface centered around the Sac3 R256/R288 residues. Other mRNA adaptor/export proteins are depicted as circles. Transition between Pol II initiation and early elongation is shown. TREX-2 attaches to the NPC basket through an NPC anchor domain comprising a 12.5 nm long Sac3 helix, two Sus1 molecules and Cdc31 (all in gray, PDB: 3fwc).
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fig7: The Sac3 PCI Domain Promotes Transcription and mRNA ExportMechanism for a relay between TREX-2, Mediator, and Pol II. Model depicts the putative overall topology of TREX-2 and its interaction with Mediator. (1) Docking to Mediator involves the conserved pair of Sac3 R256/R288 residues (red sticks) and the Med31 submodule (magenta). (2) TREX-2 regulates Cdk8 kinase module association. (3) TREX-2, Cdk8, and Med31 impact on RNA Pol II CTD Ser5 phosphorylation (S5; yellow). (4) TREX-2 also influences mRNA export via the PCI surface centered around the Sac3 R256/R288 residues. Other mRNA adaptor/export proteins are depicted as circles. Transition between Pol II initiation and early elongation is shown. TREX-2 attaches to the NPC basket through an NPC anchor domain comprising a 12.5 nm long Sac3 helix, two Sus1 molecules and Cdc31 (all in gray, PDB: 3fwc).

Mentions: In this study, we describe a direct link between the TREX-2 complex and Mediator, which is key to understanding how NPC-associated adaptors modulate gene expression (Figure 7). We find that the TREX-2 complex (1) interacts with the Mediator Med31 submodule via the Sac3 PCI domain, (2) regulates Mediator association with the Cdk8 kinase, (3) impacts on Pol II CTD Ser5 phosphorylation, and (4) employs a similar, conserved Sac3 PCI domain surface to promote transcription and mRNA export. This sheds light on the biological function of TREX-2 and opens new avenues for reconstituting the interface between nuclear pores, adaptor proteins, and the core transcription machinery.


The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression.

Schneider M, Hellerschmied D, Schubert T, Amlacher S, Vinayachandran V, Reja R, Pugh BF, Clausen T, Köhler A - Cell (2015)

The Sac3 PCI Domain Promotes Transcription and mRNA ExportMechanism for a relay between TREX-2, Mediator, and Pol II. Model depicts the putative overall topology of TREX-2 and its interaction with Mediator. (1) Docking to Mediator involves the conserved pair of Sac3 R256/R288 residues (red sticks) and the Med31 submodule (magenta). (2) TREX-2 regulates Cdk8 kinase module association. (3) TREX-2, Cdk8, and Med31 impact on RNA Pol II CTD Ser5 phosphorylation (S5; yellow). (4) TREX-2 also influences mRNA export via the PCI surface centered around the Sac3 R256/R288 residues. Other mRNA adaptor/export proteins are depicted as circles. Transition between Pol II initiation and early elongation is shown. TREX-2 attaches to the NPC basket through an NPC anchor domain comprising a 12.5 nm long Sac3 helix, two Sus1 molecules and Cdc31 (all in gray, PDB: 3fwc).
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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fig7: The Sac3 PCI Domain Promotes Transcription and mRNA ExportMechanism for a relay between TREX-2, Mediator, and Pol II. Model depicts the putative overall topology of TREX-2 and its interaction with Mediator. (1) Docking to Mediator involves the conserved pair of Sac3 R256/R288 residues (red sticks) and the Med31 submodule (magenta). (2) TREX-2 regulates Cdk8 kinase module association. (3) TREX-2, Cdk8, and Med31 impact on RNA Pol II CTD Ser5 phosphorylation (S5; yellow). (4) TREX-2 also influences mRNA export via the PCI surface centered around the Sac3 R256/R288 residues. Other mRNA adaptor/export proteins are depicted as circles. Transition between Pol II initiation and early elongation is shown. TREX-2 attaches to the NPC basket through an NPC anchor domain comprising a 12.5 nm long Sac3 helix, two Sus1 molecules and Cdc31 (all in gray, PDB: 3fwc).
Mentions: In this study, we describe a direct link between the TREX-2 complex and Mediator, which is key to understanding how NPC-associated adaptors modulate gene expression (Figure 7). We find that the TREX-2 complex (1) interacts with the Mediator Med31 submodule via the Sac3 PCI domain, (2) regulates Mediator association with the Cdk8 kinase, (3) impacts on Pol II CTD Ser5 phosphorylation, and (4) employs a similar, conserved Sac3 PCI domain surface to promote transcription and mRNA export. This sheds light on the biological function of TREX-2 and opens new avenues for reconstituting the interface between nuclear pores, adaptor proteins, and the core transcription machinery.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter Campus (VBC), Dr. Bohr-Gasse 9/3, 1030 Vienna, Austria.

Show MeSH