The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression.
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.
Affiliation: Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter Campus (VBC), Dr. Bohr-Gasse 9/3, 1030 Vienna, Austria.Show MeSH
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.
Affiliation: Max F. Perutz Laboratories, Medical University of Vienna, Vienna Biocenter Campus (VBC), Dr. Bohr-Gasse 9/3, 1030 Vienna, Austria.