The multifunctional nuclear pore complex: a platform for controlling gene expression - PubMed (original) (raw)

Review

The multifunctional nuclear pore complex: a platform for controlling gene expression

Christopher Ptak et al. Curr Opin Cell Biol. 2014 Jun.

Abstract

In addition to their established roles in nucleocytoplasmic transport, the intimate association of nuclear pore complexes (NPCs) with chromatin has long led to speculation that these structures influence peripheral chromatin structure and regulate gene expression. These ideas have their roots in morphological observations, however recent years have seen the identification of physical interactions between NPCs, chromatin, and the transcriptional machinery. Key insights into the molecular functions of specific NPC proteins have uncovered roles for these proteins in transcriptional activation and elongation, mRNA processing, as well as chromatin structure and localization. Here, we review recent studies that provide further molecular detail on the role of specific NPC components as distinct platforms for these chromatin dependent processes.

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Figures

Figure 1

Figure 1

Structural organization of NPCs. NPCs are embedded within the NE at sites where the outer nuclear membrane (ONM) and inner nuclear membrane (INM) are fused. NPCs are bound to the pore membrane through the integral pore membrane proteins and amphipathic domains of core Nups. The core scaffold Nups can be grouped into two subcomplexes, the Nup84p- and Nup170p-subcomplexes, which bind the linker Nup Nic96. The core scaffold contains multiple binding sites for the FG-containing Nups. The FG portions of these Nups are unstructured and fill the central channel. Filaments also extend from the NPC core into both the cytoplasm (cytoplasmic filaments) and nucleoplasm (nuclear basket).

Figure 2

Figure 2

Structural features of the nuclear periphery**.** A. Shown is an electron micrograph of the nuclear periphery of a HeLa cell. Densely staining heterochromatin is visible adjacent to nucleoplasmic face of the inner nuclear membrane (INM). The continuity of the peripheral heterochromatin is interrupted by lesser straining euchromatin channels at positions along the NE occupied by NPCs. B. A cartoon of the interplay between chromatin and the nuclear periphery is shown. Heterochromatin associates with the INM, but is excluded from regions containing NPCs in a manner dependent upon the nuclear basket. These regions of heterochromatin exclusion contain transcriptionally active euchromatin. ONM - outer nuclear membrane

Figure 3

Figure 3

NPC-GAL gene association and transcription. A. Shifting from glucose to galactose-containing media initiates derepression and activation of GAL genes. This process is accompanied by the translocation of the locus from the nucleoplasm to NPCs in a manner dependent upon transcription factor binding to upstream activating elements in the promoter as well as the association of chromatin remodellers (SAGA) and mRNA export factors (TREX-2) with specific Nups. Cdk1p-dependent phosphorylation of Nup1p aids in facilitating its interaction with TREX-2 and stabilizes NPC-gene association. At least for GAL1, formation of this integrated complex is promoted by the removal of SUMO (Su) from Ssn6p, a member of the repressor complex, by the NPC-bound SUMO isopeptidase Ulp1p. B. Once activated, GAL genes remain associated with NPCs. 5′ and 3′ ends of these loci are linked to the nuclear basket, which is thought to induce the formation of gene loops that aide in bringing 5′ mRNA capping and 3′ processing factors to NPCs (not shown). The ORF also associates with NPCs through the formation of a highly integrated complex centered around the RNA pol II elongation complex that includes both SAGA and TREX-2. Mex67p appears to provide a bridge between the elongation complex and NPCs. The TREX-2 component Sus1p links Mex67p to the RNA pol II complex. These interactions contribute to the positioning of the ORF in close proximity to the NPC

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