The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression
Maren Schneider1, Doris Hellerschmied2, Tobias Schubert1
1Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter Campus (VBC), Dr. Bohr-Gasse 9/3, 1030 Vienna, Austria.
Cell
|August 29, 2015
Summary
The TREX-2 complex interacts with the Mediator complex to regulate gene transcription and mRNA export. This finding reveals how nuclear pore complexes influence gene expression by connecting transcription and RNA processing.
Area of Science:
- Molecular Biology
- Cell Biology
- Gene Regulation
Background:
- Nuclear pore complexes (NPCs) regulate transport between the nucleus and cytoplasm.
- The TREX-2 complex, located at the NPC basket, influences gene expression, transcription, and mRNA export.
- The precise mechanism by which TREX-2 regulates gene expression machinery remains unclear.
Purpose of the Study:
- To elucidate the mechanism by which the TREX-2 complex regulates gene expression.
- To investigate the interaction between TREX-2 and the Mediator complex, a key regulator of RNA Polymerase II (Pol II).
Main Methods:
- Structural and biochemical studies to identify TREX-2 interaction regions with Mediator.
- Analysis of Mediator complex assembly with Cdk8 kinase.
- Assessment of Pol II recruitment and phosphorylation.
- Transcriptome and phenotypic profiling to evaluate TREX-2 and Med31 interdependence.
- Investigation of TREX-2's role in mRNA export.
Main Results:
- TREX-2 directly binds the Mediator Med31/Med7N submodule via a conserved region.
- TREX-2 regulates Mediator assembly with Cdk8 kinase.
- TREX-2 is essential for Pol II recruitment and site-specific phosphorylation.
- TREX-2 and Med31 show functional interdependence at specific genes.
- TREX-2 utilizes its Mediator-interacting surface to regulate mRNA export, linking transcription and mRNA processing.
Conclusions:
- TREX-2 acts as an adaptor complex that accesses the core transcription machinery via the Mediator complex.
- TREX-2 integrates transcription initiation with early mRNA processing steps.
- This study provides mechanistic insight into how NPC-associated factors regulate gene expression.
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