Structural highlights
Function
SAC3_YEAST Component of the SAC3-THP1 complex, which functions in transcription-coupled mRNA export from the nucleus to the cytoplasm. SAC3-THP1 functions in docking export-competent ribonucleoprotein particles (mRNPs) to the nuclear entrance of the nuclear pore complex (nuclear basket), by association with components of the nuclear mRNA export machinery (MEX67-MTR2 and SUB2) in the nucleoplasm and the nucleoporin NUP1 at the nuclear basket.[1] [2]
Publication Abstract from PubMed
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.
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, Kohler A Cell. 2015 Aug 27;162(5):1016-28. doi: 10.1016/j.cell.2015.07.059. PMID:26317468[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Fischer T, Strasser K, Racz A, Rodriguez-Navarro S, Oppizzi M, Ihrig P, Lechner J, Hurt E. The mRNA export machinery requires the novel Sac3p-Thp1p complex to dock at the nucleoplasmic entrance of the nuclear pores. EMBO J. 2002 Nov 1;21(21):5843-52. PMID:12411502
- ↑ Gallardo M, Luna R, Erdjument-Bromage H, Tempst P, Aguilera A. Nab2p and the Thp1p-Sac3p complex functionally interact at the interface between transcription and mRNA metabolism. J Biol Chem. 2003 Jun 27;278(26):24225-32. Epub 2003 Apr 17. PMID:12702719 doi:http://dx.doi.org/10.1074/jbc.M302900200
- ↑ Schneider M, Hellerschmied D, Schubert T, Amlacher S, Vinayachandran V, Reja R, Pugh BF, Clausen T, Kohler A. The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression. Cell. 2015 Aug 27;162(5):1016-28. doi: 10.1016/j.cell.2015.07.059. PMID:26317468 doi:http://dx.doi.org/10.1016/j.cell.2015.07.059