The nuclear pore complex: bridging nuclear transport and gene regulation (original) (raw)

• Field, M. C. & Dacks, J. B. First and last ancestors: reconstructing evolution of the endomembrane system with ESCRTs, vesicle coat proteins, and nuclear pore complexes. Curr. Opin. Cell Biol. 21, 4–13 (2009).
  CAS PubMed Google Scholar
• Brickner, J. H. Transcriptional memory at the nuclear periphery. Curr. Opin. Cell Biol. 21, 127–133 (2009).
  CAS PubMed PubMed Central Google Scholar
• Towbin, B. D., Meister, P. & Gasser, S. M. The nuclear envelope — a scaffold for silencing? Curr. Opin. Genet. Dev. 19, 180–186 (2009).
  CAS PubMed Google Scholar
• Degrasse, J. A. et al. Evidence for a shared nuclear pore complex architecture that is conserved from the last common eukaryotic ancestor. Mol. Cell. Proteomics 8, 2119–2130 (2009). Proteomic analyses of NPC-containing fractions from a divergent eukaryote ( Trypanosoma brucei ) provide conclusive evidence that the general blueprint of NPC architecture was already established in the last common eukaryotic ancestor.
  CAS PubMed PubMed Central Google Scholar
• Suntharalingam, M. & Wente, S. R. Peering through the pore: nuclear pore complex structure, assembly, and function. Dev. Cell 4, 775–789 (2003).
  CAS PubMed Google Scholar
• Elad, N., Maimon, T., Frenkiel-Krispin, D., Lim, R. Y. & Medalia, O. Structural analysis of the nuclear pore complex by integrated approaches. Curr. Opin. Struct. Biol. 19, 226–232 (2009).
  CAS PubMed Google Scholar
• Alber, F. et al. Determining the architectures of macromolecular assemblies. Nature 450, 683–694 (2007).
  CAS PubMed Google Scholar
• Alber, F. et al. The molecular architecture of the nuclear pore complex. Nature 450, 695–701 (2007). Together with reference 7, this work describes the development of a computational method that combines a diverse set of biophysical and proteomic data to construct a comprehensive medium resolution three-dimensional map describing the relative arrangement of all components of the S. cerevisiae NPC.
  CAS PubMed Google Scholar
• Brohawn, S. G., Partridge, J. R., Whittle, J. R. & Schwartz, T. U. The nuclear pore complex has entered the atomic age. Structure 17, 1156–1168 (2009).
  CAS PubMed PubMed Central Google Scholar
• Lutzmann, M., Kunze, R., Buerer, A., Aebi, U. & Hurt, E. Modular self-assembly of a Y-shaped multiprotein complex from seven nucleoporins. EMBO J. 21, 387–397 (2002).
  CAS PubMed PubMed Central Google Scholar
• D'Angelo, M. A., Anderson, D., Richard, E. & Hetzer, M. Nuclear pores form de novo from both sides of the nuclear envelope. Science 312, 440–443 (2006).
  CAS PubMed Google Scholar
• Makio, T. et al. The nucleoporins Nup170p and Nup157p are essential for nuclear pore complex assembly. J. Cell Biol. 185, 459–473 (2009).
  CAS PubMed PubMed Central Google Scholar
• Devos, D. et al. Components of coated vesicles and nuclear pore complexes share a common molecular architecture. PLoS Biol. 2, e380 (2004).
  PubMed PubMed Central Google Scholar
• Devos, D. et al. Simple fold composition and modular architecture of the nuclear pore complex. Proc. Natl Acad. Sci. USA 103, 2172–2177 (2006).
  CAS PubMed PubMed Central Google Scholar
• Bonifacino, J. S. & Glick, B. S. The mechanisms of vesicle budding and fusion. Cell 116, 153–166 (2004).
  CAS PubMed Google Scholar
• Köhler, A. & Hurt, E. C. Exporting RNA from the nucleus to the cytoplasm. Nature Rev. Mol. Cell Biol. 8, 761–773 (2007).
  Google Scholar
• Stewart, M. Molecular mechanism of the nuclear protein import cycle. Nature Rev. Mol. Cell Biol. 8, 195–208 (2007).
  CAS Google Scholar
• Akey, C. W. & Goldfarb, D. S. Protein import through the nuclear pore complex is a multistep process. J. Cell Biol. 109, 971–982 (1989).
  CAS PubMed Google Scholar
• Nachury, M. V. & Weis, K. The direction of transport through the nuclear pore can be inverted. Proc. Natl Acad. Sci. USA 96, 9622–9627 (1999).
  CAS PubMed PubMed Central Google Scholar
• Kuersten, S., Ohno, M. & Mattaj, I. W. Nucleocytoplasmic transport: Ran, beta and beyond. Trends Cell Biol. 11, 497–503 (2001).
  CAS PubMed Google Scholar
• Terry, L. J. & Wente, S. R. Flexible gates: dynamic topologies and functions for FG nucleoporins in nucleocytoplasmic transport. Eukaryot. Cell 8, 1814–1827 (2009).
  CAS PubMed PubMed Central Google Scholar
• Radu, A., Moore, M. S. & Blobel, G. The peptide repeat domain of nucleoporin Nup98 functions as a docking site in transport across the nuclear pore complex. Cell 81, 215–222 (1995).
  CAS PubMed Google Scholar
• Bayliss, R., Littlewood, T. & Stewart, M. Structural basis for the interaction between FxFG nucleoporin repeats and importin-β in nuclear trafficking. Cell 102, 99–108 (2000).
  CAS PubMed Google Scholar
• Denning, D. P. & Rexach, M. F. Rapid evolution exposes the boundaries of domain structure and function in natively unfolded FG nucleoporins. Mol. Cell. Proteomics 6, 272–282 (2007).
  CAS PubMed Google Scholar
• Rout, M. P. et al. The yeast nuclear pore complex: composition, architecture, and transport mechanism. J. Cell Biol. 148, 635–651 (2000).
  CAS PubMed PubMed Central Google Scholar
• Cronshaw, J. M., Krutchinsky, A. N., Zhang, W., Chait, B. T. & Matunis, M. J. Proteomic analysis of the mammalian nuclear pore complex. J. Cell Biol. 158, 915–927 (2002). Mass spectrometry analysis defines the proteome of the mammalian NPC for the first time and paves the way for a more detailed characterization of NPC structure and function.
  CAS PubMed PubMed Central Google Scholar
• Denning, D. P., Patel, S. S., Uversky, V., Fink, A. L. & Rexach, M. Disorder in the nuclear pore complex: the FG repeat regions of nucleoporins are natively unfolded. Proc. Natl Acad. Sci. USA 100, 2450–2455 (2003).
  CAS PubMed PubMed Central Google Scholar
• Lim, R. Y. et al. Flexible phenylalanine-glycine nucleoporins as entropic barriers to nucleocytoplasmic transport. Proc. Natl Acad. Sci. USA 103, 9512–9517 (2006).
  CAS PubMed PubMed Central Google Scholar
• Patel, S. S., Belmont, B. J., Sante, J. M. & Rexach, M. F. Natively unfolded nucleoporins gate protein diffusion across the nuclear pore complex. Cell 129, 83–96 (2007).
  CAS PubMed Google Scholar
• Jovanovic-Talisman, T. et al. Artificial nanopores that mimic the transport selectivity of the nuclear pore complex. Nature 457, 1023–1027 (2009).
  CAS PubMed Google Scholar
• Akey, C. W. Visualization of transport-related configurations of the nuclear pore transporter. Biophys. J. 58, 341–355 (1990).
  CAS PubMed PubMed Central Google Scholar
• Rexach, M. & Blobel, G. Protein import into nuclei: association and dissociation reactions involving transport substrate, transport factors, and nucleoporins. Cell 83, 683–692 (1995).
  CAS PubMed Google Scholar
• Ben-Efraim, I. & Gerace, L. Gradient of increasing affinity of importin β for nucleoporins along the pathway of nuclear import. J. Cell Biol. 152, 411–417 (2001).
  CAS PubMed PubMed Central Google Scholar
• Strawn, L. A., Shen, T., Shulga, N., Goldfarb, D. S. & Wente, S. R. Minimal nuclear pore complexes define FG repeat domains essential for transport. Naure. Cell Biol. 6, 197–206 (2004).
  CAS Google Scholar
• Rout, M. P., Aitchison, J. D., Magnasco, M. O. & Chait, B. T. Virtual gating and nuclear transport: the hole picture. Trends Cell Biol. 13, 622–628 (2003).
  CAS PubMed Google Scholar
• Peters, R. Translocation through the nuclear pore: Kaps pave the way. Bioessays 31, 466–477 (2009). Excellent introductory review describing current nuclear transport models in the light of the latest data obtained by single transporter recording, optical super-resolution microscopy and transport assays on artificial nanopores.
  CAS PubMed Google Scholar
• Lim, R. Y. et al. Nanomechanical basis of selective gating by the nuclear pore complex. Science 318, 640–643 (2007).
  CAS PubMed Google Scholar
• Ribbeck, K. & Gorlich, D. The permeability barrier of nuclear pore complexes appears to operate via hydrophobic exclusion. EMBO J. 21, 2664–2671 (2002).
  CAS PubMed PubMed Central Google Scholar
• Frey, S., Richter, R. P. & Görlich, D. FG-rich repeats of nuclear pore proteins form a three-dimensional meshwork with hydrogel-like properties. Science 314, 815–817 (2006).
  CAS PubMed Google Scholar
• Frey, S. & Görlich, D. A saturated FG-repeat hydrogel can reproduce the permeability properties of nuclear pore complexes. Cell 130, 512–523 (2007).
  CAS PubMed Google Scholar
• Mohr, D., Frey, S., Fischer, T., Guttler, T. & Gorlich, D. Characterisation of the passive permeability barrier of nuclear pore complexes. EMBO J. 28, 2541–2553 (2009).
  CAS PubMed PubMed Central Google Scholar
• Ader, C. et al. Amyloid-like interactions within nucleoporin FG hydrogels. Proc. Natl Acad. Sci. USA 107, 6281–6285 (2010).
  CAS PubMed PubMed Central Google Scholar
• Macara, I. G. Transport into and out of the nucleus. Microbiol Mol. Biol. Rev. 65, 570–594 (2001).
  CAS PubMed PubMed Central Google Scholar
• Krishnan, V. V. et al. Intramolecular cohesion of coils mediated by phenylalanine–glycine motifs in the natively unfolded domain of a nucleoporin. PLoS Comput. Biol. 4, e1000145 (2008).
  CAS PubMed PubMed Central Google Scholar
• Miao, L. & Schulten, K. Transport-related structures and processes of the nuclear pore complex studied through molecular dynamics. Structure 17, 449–459 (2009).
  CAS PubMed PubMed Central Google Scholar
• Timney, B. et al. Simple kinetic relationships and nonspecific competition govern nuclear import rates in vivo. J. Cell Biol. 175, 579–593 (2006).
  CAS PubMed PubMed Central Google Scholar
• Zilman, A., Di Talia, S., Chait, B. T., Rout, M. P. & Magnasco, M. O. Efficiency, selectivity, and robustness of nucleocytoplasmic transport. PLoS Comput. Biol. 3, e125 (2007).
  PubMed PubMed Central Google Scholar
• Engelhardt, P. & Pusa, K. Nuclear pore complexes: “press-stud” elements of chromosomes in pairing and control. Nature New Biol. 240, 163–166 (1972).
  CAS PubMed Google Scholar
• Blobel, G. Gene gating: a hypothesis. Proc. Natl Acad. Sci. USA 82, 8527–8529 (1985). The first formulation of the hypothesis that NPCs serve as gene-gating organelles that are capable of interacting specifically with transcriptionally active portions of the genome.
  CAS PubMed PubMed Central Google Scholar
• Kehlenbach, R. H., Dickmanns, A., Kehlenbach, A., Guan, T. & Gerace, L. A role for RanBP1 in the release of CRM1 from the nuclear pore complex in a terminal step of nuclear export. J. Cell Biol. 145, 645–657 (1999).
  CAS PubMed PubMed Central Google Scholar
• Schmitt, C. et al. Dbp5, a DEAD-box protein required for mRNA export, is recruited to the cytoplasmic fibrils of nuclear pore complex via a conserved interaction with CAN/Nup159p. EMBO J. 18, 4332–4347 (1999).
  CAS PubMed PubMed Central Google Scholar
• Stelter, P. et al. Molecular basis for the functional interaction of dynein light chain with the nuclear-pore complex. Nature Cell Biol. 9, 788–796 (2007).
  CAS PubMed Google Scholar
• Carmody, S. R. & Wente, S. R. mRNA nuclear export at a glance. J. Cell Sci. 122, 1933–1937 (2009).
  CAS PubMed PubMed Central Google Scholar
• Minakhina, S., Myers, R., Druzhinina, M. & Steward, R. Crosstalk between the actin cytoskeleton and Ran-mediated nuclear transport. BMC Cell Biol. 6, 32 (2005).
  PubMed PubMed Central Google Scholar
• Hutten, S., Walde, S., Spillner, C., Hauber, J. & Kehlenbach, R. H. The nuclear pore component Nup358 promotes transportin-dependent nuclear import. J. Cell Sci. 122, 1100–1110 (2009).
  CAS PubMed Google Scholar
• Stewart, M. Ratcheting mRNA out of the nucleus. Mol. Cell 25, 327–330 (2007).
  CAS PubMed Google Scholar
• Wu, J., Matunis, M. J., Kraemer, D., Blobel, G. & Coutavas, E. Nup358, a cytoplasmically exposed nucleoporin with peptide repeats, Ran-GTP binding sites, zinc fingers, a cyclophilin A homologous domain, and a leucine-rich region. J. Biol. Chem. 270, 14209–14213 (1995).
  CAS PubMed Google Scholar
• Matunis, M. J., Wu, J. & Blobel, G. SUMO-1 modification and its role in targeting the Ran GTPase-activating protein, RanGAP1, to the nuclear pore complex. J. Cell Biol. 140, 499–509 (1998).
  CAS PubMed PubMed Central Google Scholar
• Saitoh, N. et al. In situ SUMOylation analysis reveals a modulatory role of RanBP2 in the nuclear rim and PML bodies. Exp. Cell Res. 312, 1418–1430 (2006).
  CAS PubMed Google Scholar
• Reverter, D. & Lima, C. D. Insights into E3 ligase activity revealed by a SUMO-RanGAP1-Ubc9-Nup358 complex. Nature 435, 687–692 (2005).
  CAS PubMed PubMed Central Google Scholar
• Radtke, K., Döhner, K. & Sodeik, B. Viral interactions with the cytoskeleton: a hitchhiker's guide to the cell. Cell. Microbiol 8, 387–400 (2006).
  CAS PubMed Google Scholar
• Roth, D. M., Moseley, G. W., Glover, D., Pouton, C. W. & Jans, D. A. A microtubule-facilitated nuclear import pathway for cancer regulatory proteins. Traffic 8, 673–686 (2007).
  CAS PubMed Google Scholar
• Singer, R. H. Highways for mRNA transport. Cell 134, 722–723 (2008).
  CAS PubMed PubMed Central Google Scholar
• Joseph, J. & Dasso, M. The nucleoporin Nup358 associates with and regulates interphase microtubules. FEBS Lett. 582, 190–196 (2008).
  CAS PubMed Google Scholar
• Cho, K. I. et al. RANBP2 is an allosteric activator of the conventional kinesin-1 motor protein, KIF5B, in a minimal cell-free system. EMBO Rep. 10, 480–486 (2009).
  CAS PubMed PubMed Central Google Scholar
• Ris, H. Three-dimensional imaging of cell ultrastructure with high resolution, low voltage SEM. Int. Phys. Conf. Ser. 98, 657–662 (1989).
  Google Scholar
• Jarnik, M. & Aebi, U. Toward a more complete 3-D structure of the nuclear pore complex. J. Struct. Biol. 107, 291–308 (1991).
  CAS PubMed Google Scholar
• Ris, H. & Malecki, M. High-resolution field emission scanning electron microscope imaging of internal cell structures after Epon extraction from sections: a new approach to correlative ultrastructural and immunocytochemical studies. J. Struct. Biol. 111, 148–157 (1993).
  CAS PubMed Google Scholar
• Goldberg, M. W. & Allen, T. D. High resolution scanning electron microscopy of the nuclear envelope: demonstration of a new, regular, fibrous lattice attached to the baskets of the nucleoplasmic face of the nuclear pores. J. Cell Biol. 119, 1429–1440 (1992). References 68 and 69 were among the first to provide clear structural evidence for the presence of a basket structure anchored to the nucleoplasmic face of the NPC and the existence of interconnecting fibrils spanning the distance between neighbouring nuclear pores, stretching both perpendicularly and in parallel to the nuclear envelope.
  CAS PubMed Google Scholar
• Stoffler, D., Goldie, K. N., Feja, B. & Aebi, U. Calcium-mediated structural changes of native nuclear pore complexes monitored by time-lapse atomic force microscopy. J. Mol. Biol. 287, 741–752 (1999).
  CAS PubMed Google Scholar
• Beck, M., Lucicc´, V., Förster, F., Baumeister, W. & Medalia, O. Snapshots of nuclear pore complexes in action captured by cryo-electron tomography. Nature 449, 611–615 (2007).
  CAS PubMed Google Scholar
• Kiseleva, E. et al. Yeast nuclear pore complexes have a cytoplasmic ring and internal filaments. J. Struct. Biol. 145, 272–288 (2004).
  CAS PubMed Google Scholar
• Daneholt, B. A look at messenger RNP moving through the nuclear pore. Cell 88, 585–588 (1997).
  CAS PubMed Google Scholar
• Kiseleva, E., Goldberg, M. W., Allen, T. D. & Akey, C. W. Active nuclear pore complexes in Chironomus: visualization of transporter configurations related to mRNP export. J. Cell Sci. 111, 223–236 (1998).
  CAS PubMed Google Scholar
• Soop, T. et al. Nup153 affects entry of messenger and ribosomal ribonucleoproteins into the nuclear basket during export. Mol. Biol. Cell 16, 5610–5620 (2005).
  CAS PubMed PubMed Central Google Scholar
• Kylberg, K. et al. Exclusion of mRNPs and ribosomal particles from a thin zone beneath the nuclear envelope revealed upon inhibition of transport. Exp. Cell Res. 316, 1028–1038 (2009). The nucleocytoplasmic transport of RNPs was examined by EM, revealing the presence of a basket-dependent 'exclusion-zone' lining the entire extent of the nuclear face of the nuclear envelope, which prevents unwanted macromolecules from encroaching on the nuclear transport channel.
  PubMed Google Scholar
• Krull, S. et al. Protein Tpr is required for establishing nuclear pore-associated zones of heterochromatin exclusion. EMBO J. 29, 1659–1673 (2010). RNA interference experiments were combined with EM analyses to show that the basket component TPR is involved in forming NPC-associated heterochromatin exclusion zones along the nuclear surface of the nuclear envelope, thus preventing macromolecular structures from interfering with nuclear transport.
  CAS PubMed PubMed Central Google Scholar
• Byrd, D. A. et al. Tpr, a large coiled coil protein whose amino terminus is involved in activation of oncogenic kinases, is localized to the cytoplasmic surface of the nuclear pore complex. J. Cell Biol. 127, 1515–1526 (1994).
  CAS PubMed Google Scholar
• Kuznetsov, N. V. et al. The evolutionarily conserved single-copy gene for murine Tpr encodes one prevalent isoform in somatic cells and lacks paralogs in higher eukaryotes. Chromosoma 111, 236–255 (2002).
  CAS PubMed Google Scholar
• Zimowska, G., Aris, J. P. & Paddy, M. R. A Drosophila Tpr protein homolog is localized both in the extrachromosomal channel network and to nuclear pore complexes. J. Cell Sci. 110, 927–944 (1997).
  CAS PubMed Google Scholar
• Qi, H. et al. Megator, an essential coiled-coil protein that localizes to the putative spindle matrix during mitosis in Drosophila. Mol. Biol. Cell 15, 4854–4865 (2004).
  CAS PubMed PubMed Central Google Scholar
• Strambio-de-Castillia, C., Blobel, G. & Rout, M. P. Proteins connecting the nuclear pore complex with the nuclear interior. J. Cell Biol. 144, 839–855 (1999).
  CAS PubMed PubMed Central Google Scholar
• Frosst, P., Guan, T., Subauste, C., Hahn, K. & Gerace, L. Tpr is localized within the nuclear basket of the pore complex and has a role in nuclear protein export. J. Cell Biol. 156, 617–630 (2002).
  CAS PubMed PubMed Central Google Scholar
• Krull, S., Thyberg, J., Björkroth, B., Rackwitz, H. R. & Cordes, V. C. Nucleoporins as components of the nuclear pore complex core structure and Tpr as the architectural element of the nuclear basket. Mol. Biol. Cell 15, 4261–4277 (2004).
  CAS PubMed PubMed Central Google Scholar
• Cordes, V. C., Reidenbach, S., Rackwitz, H. R. & Franke, W. W. Identification of protein p270/Tpr as a constitutive component of the nuclear pore complex-attached intranuclear filaments. J. Cell Biol. 136, 515–529 (1997).
  CAS PubMed PubMed Central Google Scholar
• Hase, M. E., Kuznetsov, N. V. & Cordes, V. C. Amino acid substitutions of coiled-coil protein Tpr abrogate anchorage to the nuclear pore complex but not parallel, in-register homodimerization. Mol. Biol. Cell 12, 2433–2452 (2001).
  CAS PubMed PubMed Central Google Scholar
• Galy, V. et al. Nuclear retention of unspliced mRNAs in yeast is mediated by perinuclear Mlp1. Cell 116, 63–73 (2004).
  CAS PubMed Google Scholar
• Zhao, X., Wu, C. Y. & Blobel, G. Mlp-dependent anchorage and stabilization of a desumoylating enzyme is required to prevent clonal lethality. J. Cell Biol. 167, 605–611 (2004).
  CAS PubMed PubMed Central Google Scholar
• Casolari, J. M., Brown, C. R., Drubin, D. A., Rando, O. J. & Silver, P. A. Developmentally induced changes in transcriptional program alter spatial organization across chromosomes. Genes Dev. 19, 1188–1198 (2005). Changes in nuclear organization that follow stimulation of S. cerevisiae cells by mating pheromone were studied to show that the yeast TPR homologue, Mlp1, has a role in determining nuclear organization in response to a developmental cue.
  CAS PubMed PubMed Central Google Scholar
• Niepel, M., Strambio-de-Castillia, C., Fasolo, J., Chait, B. T. & Rout, M. P. The nuclear pore complex-associated protein, Mlp2p, binds to the yeast spindle pole body and promotes its efficient assembly. J. Cell Biol. 170, 225–235 (2005).
  CAS PubMed PubMed Central Google Scholar
• Vinciguerra, P., Iglesias, N., Camblong, J., Zenklusen, D. & Stutz, F. Perinuclear Mlp proteins downregulate gene expression in response to a defect in mRNA export. EMBO J. 24, 813–823 (2005). Chromatin immunoprecipitation, FISH and pulse-chase experiments were used to show that yeast TPR-like proteins help recruit nascent transcripts to the NPC and have a role in coupling mRNA biogenesis with export through the NPC.
  CAS PubMed PubMed Central Google Scholar
• Lewis, A., Felberbaum, R. & Hochstrasser, M. A nuclear envelope protein linking nuclear pore basket assembly, SUMO protease regulation, and mRNA surveillance. J. Cell Biol. 178, 813–827 (2007).
  CAS PubMed PubMed Central Google Scholar
• Palancade, B. et al. Nucleoporins prevent DNA damage accumulation by modulating Ulp1-dependent sumoylation processes. Mol. Biol. Cell 18, 2912–2923 (2007).
  CAS PubMed PubMed Central Google Scholar
• Xu, X. M. et al. NUCLEAR PORE ANCHOR, the Arabidopsis homolog of Tpr/Mlp1/Mlp2/megator, is involved in mRNA export and SUMO homeostasis and affects diverse aspects of plant development. Plant Cell 19, 1537–1548 (2007).
  CAS PubMed PubMed Central Google Scholar
• Lee, S. H., Sterling, H., Burlingame, A. & McCormick, F. Tpr directly binds to Mad1 and Mad2 and is important for the Mad1-Mad2-mediated mitotic spindle checkpoint. Genes Dev. 22, 2926–2931 (2008).
  CAS PubMed PubMed Central Google Scholar
• De Souza, C. P., Hashmi, S. B., Nayak, T., Oakley, B. & Osmani, S. A. Mlp1 acts as a mitotic scaffold to spatially regulate spindle assembly checkpoint proteins in Aspergillus nidulans. Mol. Biol. Cell 20, 2146–2159 (2009).
  CAS PubMed PubMed Central Google Scholar
• Lince-Faria, M. et al. Spatiotemporal control of mitosis by the conserved spindle matrix protein Megator. J. Cell Biol. 184, 647–657 (2009). Megator, the D. melanogaster homologue of human TPR, is shown here to specifically interact with SAC proteins, thus mediating normal mitotic duration and checkpoint response.
  CAS PubMed PubMed Central Google Scholar
• Skruzný, M. et al. An endoribonuclease functionally linked to perinuclear mRNP quality control associates with the nuclear pore complexes. PLoS Biol. 7, e8 (2009).
  PubMed Google Scholar
• Tan-Wong, S. M., Wijayatilake, H. D. & Proudfoot, N. J. Gene loops function to maintain transcriptional memory through interaction with the nuclear pore complex. Genes Dev. 23, 2610–2624 (2009).
  CAS PubMed PubMed Central Google Scholar
• Ahmed, S. et al. DNA zip codes control an ancient mechanism for gene targeting to the nuclear periphery. Nature Cell Biol. 12, 111–118 (2010). Identification of specific gene-recuitment sequences, which function as DNA zip codes to recruit inducible S. cerevisiae genes from the nucleoplasm to the NPC and are required for full transcriptional activation of a subset of genes involved in adaptation to varying environmental conditions.
  CAS PubMed Google Scholar
• Vaquerizas, J. M. et al. Nuclear pore proteins Nup153 and Megator define transcriptionally active regions in the Drosophila genome. PLoS Genet. 6, e1000846 (2010). Using chromatin immunoprecipitation combined with microarray hybridization, it was shown that the NPC acts as a global gene regulator in D. melanogaster by interacting with Nup-associated regions of the genome and thereby promoting chromosomal organization and transcriptional control.
  PubMed PubMed Central Google Scholar
• Vinciguerra, P. & Stutz, F. mRNA export: an assembly line from genes to nuclear pores. Curr. Opin. Cell Biol. 16, 285–292 (2004).
  CAS PubMed Google Scholar
• Skaggs, H. S. et al. HSF1-TPR interaction facilitates export of stress-induced HSP70 mRNA. J. Biol. Chem. 282, 33902–33907 (2007).
  CAS PubMed Google Scholar
• Fasken, M. B. & Corbett, A. H. Mechanisms of nuclear mRNA quality control. RNA Biol. 6, 237–241 (2009).
  CAS PubMed Google Scholar
• Akhtar, A. & Gasser, S. M. The nuclear envelope and transcriptional control. Nature Rev. Genet. 8, 507–517 (2007).
  CAS PubMed Google Scholar
• Chekanova, J. A., Abruzzi, K. C., Rosbash, M. & Belostotsky, D. A. Sus1, Sac3, and Thp1 mediate post-transcriptional tethering of active genes to the nuclear rim as well as to non-nascent mRNP. RNA 14, 66–77 (2008).
  CAS PubMed PubMed Central Google Scholar
• Schmid, M. & Jensen, T. H. Quality control of mRNP in the nucleus. Chromosoma 117, 419–429 (2008).
  CAS PubMed Google Scholar
• Schmid, M. & Jensen, T. H. The exosome: a multipurpose RNA-decay machine. Trends Biochem. Sci. 33, 501–510 (2008).
  CAS PubMed Google Scholar
• Dziembowski, A. et al. Proteomic analysis identifies a new complex required for nuclear pre-mRNA retention and splicing. EMBO J. 23, 4, 847–856 (2004).
  Google Scholar
• Lieberman-Aiden, E. et al. Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326, 289–293 (2009).
  CAS PubMed PubMed Central Google Scholar
• Andrulis, E. D., Neiman, A. M., Zappulla, D. C. & Sternglanz, R. Perinuclear localization of chromatin facilitates transcriptional silencing. Nature 394, 592–595 (1998).
  CAS PubMed Google Scholar
• Kosak, S. T. et al. Subnuclear compartmentalization of immunoglobulin loci during lymphocyte development. Science 296, 158–162 (2002).
  CAS PubMed Google Scholar
• Sexton, T., Schober, H., Fraser, P. & Gasser, S. M. Gene regulation through nuclear organization. Nature Struct. Mol. Biol. 14, 1049–1055 (2007).
  CAS Google Scholar
• Dilworth, D. J. et al. The mobile nucleoporin Nup2p and chromatin-bound Prp20p function in endogenous NPC-mediated transcriptional control. J. Cell Biol. 171, 955–965 (2005). Results obtained from proteomics, genomics and functional assays of boundary activity and epigenetic variegation suggest that the NPC plays an active part in chromatin organization by facilitating the transition of chromatin between activity states.
  CAS PubMed PubMed Central Google Scholar
• Dieppois, G., Iglesias, N. & Stutz, F. Cotranscriptional recruitment to the mRNA export receptor Mex67p contributes to nuclear pore anchoring of activated genes. Mol. Cell. Biol. 26, 7, 858–870 (2006).
  Google Scholar
• Schmid, M. et al. Nup-PI: the nucleopore-promoter interaction of genes in yeast. Mol. Cell 21, 379–391 (2006).
  CAS PubMed Google Scholar
• Taddei, A. et al. Nuclear pore association confers optimal expression levels for an inducible yeast gene. Nature 441, 774–778 (2006).
  CAS PubMed Google Scholar
• Brickner, D. G. et al. H2A.Z-mediated localization of genes at the nuclear periphery confers epigenetic memory of previous transcriptional state. PLoS Biol. 5, e81 (2007).
  PubMed PubMed Central Google Scholar
• Ishii, K., Arib, G., Lin, C., Van Houwe, G. & Laemmli, U. K. Chromatin boundaries in budding yeast: the nuclear pore connection. Cell 109, 551–562 (2002). Genetic studies, immunolocalization, live imaging and chromatin immunoprecipitation experiments conducted on chromatin boundary activities identified in S. cerevisiae provided the initial evidence that tethering of genomic loci to the NPC can dramatically alter their epigenetic activity.
  CAS PubMed Google Scholar
• Brickner, J. H. & Walter, P. Gene recruitment of the activated INO1 locus to the nuclear membrane. PLoS Biol. 2, e342 (2004).
  PubMed PubMed Central Google Scholar
• Kundu, S., Horn, P. J. & Peterson, C. L. SWI/SNF is required for transcriptional memory at the yeast GAL gene cluster. Genes Dev. 21, 997–1004 (2007).
  CAS PubMed PubMed Central Google Scholar
• Kundu, S. & Peterson, C. L. Dominant role for signal transduction in transcriptional memory of yeast GAL genes. Mol. Cell. Biol. 30, 2330–2340 (2010).
  CAS PubMed PubMed Central Google Scholar
• Taddei, A. et al. Nuclear pore association confers optimal expression levels for an inducible yeast gene. Nature 441, 774–778 (2006).
  CAS PubMed Google Scholar
• Cabal, G. et al. SAGA interacting factors confine sub-diffusion of transcribed genes to the nuclear envelope. Nature 441, 770–773 (2006).
  CAS PubMed Google Scholar
• Kurshakova, M. M. et al. SAGA and a novel Drosophila export complex anchor efficient transcription and mRNA export to NPC. EMBO J. 26, 4, 956–965 (2007).
  Google Scholar
• Luthra, R. et al. Actively transcribed GAL genes can be physically linked to the nuclear pore by the SAGA chromatin modifying complex. J. Biol. Chem. 282, 3042–3049 (2007).
  CAS PubMed Google Scholar
• Köhler, A., Schneider, M., Cabal, G. G., Nehrbass, U. & Hurt, E. Yeast Ataxin-7 links histone deubiquitination with gene gating and mRNA export. Nature Cell Biol. 10, 707–715 (2008).
  PubMed Google Scholar
• Rouge-maille, M. et al. THO/Sub2p functions to coordinate 3′-end processing with gene-nuclear pore association. Cell 135, 308–321 (2008).
  CAS Google Scholar
• Jani, D. et al. Sus1, Cdc31, and the Sac3 CID region form a conserved interaction platform that promotes nuclear pore association and mRNA export. Mol. Cell 33, 727–737 (2009).
  CAS PubMed PubMed Central Google Scholar
• Klockner, C. et al. Mutational uncoupling of the role of Sus1 in nuclear pore complex targeting of an mRNA export complex and histone H2B deubiquitination. J. Biol. Chem. 284, 12049–12056 (2009).
  PubMed PubMed Central Google Scholar
• Ellisdon, A. M., Jani, D., Kohler, A., Hurt, E. & Stewart, M. Structural basis for the interaction between yeast Spt-Ada-Gcn5 acetyltransferase (SAGA) complex components Sgf11 and Sus1. J. Biol. Chem. 285, 3850–3856 (2010).
  CAS PubMed Google Scholar
• Hutchison, N. & Weintraub, H. Localization of DNAase I-sensitive sequences to specific regions of interphase nuclei. Cell 43, 471–482 (1985).
  CAS PubMed Google Scholar
• Ragoczy, T., Bender, M. A., Telling, A., Byron, R. & Groudine, M. The locus control region is required for association of the murine β-globin locus with engaged transcription factories during erythroid maturation. Genes Dev. 20, 1447–1457 (2006).
  CAS PubMed PubMed Central Google Scholar
• Donze, D. & Kamakaka, R. T. Braking the silence: how heterochromatic gene repression is stopped in its tracks. Bioessays 24, 344–349 (2002).
  CAS PubMed Google Scholar
• Capelson, M. et al. Chromatin-bound nuclear pore components regulate gene expression in higher eukaryotes. Cell 140, 372–383 (2010).
  CAS PubMed PubMed Central Google Scholar
• Kalverda, B., Pickersgill, H., Shloma, V. V. & Fornerod, M. Nucleoporins directly stimulate expression of developmental and cell-cycle genes inside the nucleoplasm. Cell 140, 360–371 (2010).
  CAS PubMed Google Scholar
• Therizols, P. et al. Telomere tethering at the nuclear periphery is essential for efficient DNA double strand break repair in subtelomeric region. J. Cell Biol. 172, 189–199 (2006).
  CAS PubMed PubMed Central Google Scholar
• Zhao, X. & Blobel, G. A SUMO ligase is part of a nuclear multiprotein complex that affects DNA repair and chromosomal organization. Proc. Natl Acad. Sci. USA 102, 4777–4782 (2005).
  CAS PubMed PubMed Central Google Scholar
• Nagai, S. et al. Functional targeting of DNA damage to a nuclear pore-associated SUMO-dependent ubiquitin ligase. Science 322, 597–602 (2008).
  CAS PubMed PubMed Central Google Scholar
• Ii, T., Mullen, J. R., Slagle, C. E. & Brill, S. J. Stimulation of in vitro sumoylation by Slx5-Slx8: evidence for a functional interaction with the SUMO pathway. DNA Repair 6, 1679–1691 (2007).
  CAS PubMed PubMed Central Google Scholar
• Oza, P. & Peterson, C. L. Opening the DNA repair toolbox: localization of DNA double strand breaks to the nuclear periphery. Cell Cycle 9, 43–49 (2010).
  CAS PubMed Google Scholar
• Khadaroo, B. et al. The DNA damage response at eroded telomeres and tethering to the nuclear pore complex. Nature Cell Biol. 11, 980–987 (2009). Single-cell analysis was used to show that double-stranded DNA breaks get recruited to the vicinity of the NPC where they can undergo specialized repair in an environment designed to favour chromatin stability.
  CAS PubMed Google Scholar
• Hanawalt, P. C. Controlling the efficiency of excision repair. Mutat. Res. 485, 3–13 (2001).
  CAS PubMed Google Scholar
• Gaillard, H. et al. Genome-wide analysis of factors affecting transcription elongation and DNA repair: a new role for PAF and Ccr4-Not in transcription-coupled repair. PLoS Genet. 5, e1000364 (2009).
  PubMed PubMed Central Google Scholar
• Zhang, L., Jones, K. & Gong, F. The molecular basis of chromatin dynamics during nucleotide excision repair. Biochem. Cell Biol. 87, 265–272 (2009).
  CAS PubMed Google Scholar
• Faza, M. B. et al. Sem1 is a functional component of the nuclear pore complex-associated messenger RNA export machinery. J. Cell Biol. 184, 833–846 (2009).
  CAS PubMed PubMed Central Google Scholar
• Fernandez-Martinez, J. & Rout, M. P. Nuclear pore complex biogenesis. Curr. Opin. Cell Biol., 21, 603–612 (2009).
  CAS PubMed PubMed Central Google Scholar
• Guttinger, S., Laurell, E. & Kutay, U. Orchestrating nuclear envelope disassembly and reassembly during mitosis. Nature Rev. Mol. Cell Biol. 10, 178–191 (2009).
  Google Scholar
• Iouk, T., Kerscher, O., Scott, R. J., Basrai, M. A. & Wozniak, R. W. The yeast nuclear pore complex functionally interacts with components of the spindle assembly checkpoint. J. Cell Biol. 159, 807–819 (2002).
  CAS PubMed PubMed Central Google Scholar
• Gillett, E. S., Espelin, C. W. & Sorger, P. K. Spindle checkpoint proteins and chromosome-microtubule attachment in budding yeast. J. Cell Biol. 164, 535–546 (2004).
  CAS PubMed PubMed Central Google Scholar
• Scott, R. J., Lusk, C. P., Dilworth, D. J., Aitchison, J. D. & Wozniak, R. W. Interactions between Mad1p and the nuclear transport machinery in the yeast Saccharomyces cerevisiae. Mol. Biol. Cell 16, 4362–4374 (2005).
  CAS PubMed PubMed Central Google Scholar
• Scott, R. J., Cairo, L. V., Van de Vosse, D. W. & Wozniak, R. W. The nuclear export factor Xpo1p targets Mad1p to kinetochores in yeast. J. Cell Biol. 184, 21–29 (2009).
  CAS PubMed PubMed Central Google Scholar
• Katsani, K. R., Karess, R. E., Dostatni, N. & Doye, V. In vivo dynamics of Drosophila nuclear envelope components. Mol. Biol. Cell 19, 3652–3666 (2008).
  CAS PubMed PubMed Central Google Scholar
• Nakano, H., Funasaka, T., Hashizume, C. & Wong, R. W. Nucleoporin Tpr associates with dynein complex preventing chromosome lagging formation during mitosis. J. Biol. Chem. 285, 10841–10849 (2010).
  CAS PubMed PubMed Central Google Scholar
• Rao, C. V., Yamada, H. Y., Yao, Y. & Dai, W. Enhanced genomic instabilities caused by deregulated microtubule dynamics and chromosome segregation: a perspective from genetic studies in mice. Carcinogenesis 30, 1469–1474 (2009).
  CAS PubMed PubMed Central Google Scholar
• Pemberton, L. F. & Paschal, B. M. Mechanisms of receptor-mediated nuclear import and nuclear export. Traffic 6, 187–198 (2005).
  CAS PubMed Google Scholar
• Tran, E. J., Bolger, T. A. & Wente, S. R. SnapShot: nuclear transport. Cell 131, 420 (2007).
  PubMed Google Scholar
• Cullen, B. R. Viral RNAs: lessons from the enemy. Cell 136, 592–597 (2009).
  CAS PubMed PubMed Central Google Scholar
• Oza, P., Jaspersen, S. L., Miele, A., Dekker, J. & Peterson, C. L. Mechanisms that regulate localization of a DNA double-strand break to the nuclear periphery. Genes Dev. 23, 912–927 (2009).
  CAS PubMed PubMed Central Google Scholar
• Schober, H., Ferreira, H., Kalck, V., Gehlen, L. R. & Gasser, S. M. Yeast telomerase and the SUN domain protein Mps3 anchor telomeres and repress subtelomeric recombination. Genes Dev. 23, 928–938 (2009).
  CAS PubMed PubMed Central Google Scholar
• Jaspersen, S. L., Giddings, T. H. & Winey, M. Mps3p is a novel component of the yeast spindle pole body that interacts with the yeast centrin homologue Cdc31p. J. Cell Biol. 159, 945–956 (2002).
  CAS PubMed PubMed Central Google Scholar
• Ding, X. et al. SUN1 is required for telomere attachment to nuclear envelope and gametogenesis in mice. Dev. Cell 12, 863–872 (2007).
  CAS PubMed Google Scholar
• Gartenberg, M. R. Life on the edge: telomeres and persistent DNA breaks converge at the nuclear periphery. Genes Dev. 23, 1027–1031 (2009).
  CAS PubMed PubMed Central Google Scholar
• Liu, Q. et al. Functional association of Sun1 with nuclear pore complexes. J. Cell Biol. 178, 785–798 (2007).
  CAS PubMed PubMed Central Google Scholar
• Mekhail, K., Seebacher, J., Gygi, S. P. & Moazed, D. Role for perinuclear chromosome tethering in maintenance of genome stability. Nature 456, 667–670 (2008).
  CAS PubMed PubMed Central Google Scholar
• Mans, B. J., Anantharaman, V., Aravind, L. & Koonin, E. V. Comparative genomics, evolution and origins of the nuclear envelope and nuclear pore complex. Cell Cycle 3, 1612–1637 (2004).
  CAS PubMed Google Scholar
• Grund, S. E. et al. The inner nuclear membrane protein Src1 associates with subtelomeric genes and alters their regulated gene expression. J. Cell Biol. 182, 897–910 (2008).
  CAS PubMed PubMed Central Google Scholar
• Gonzalez-Barrera, S., Garcia-Rubio, M. & Aguilera, A. Transcription and double-strand breaks induce similar mitotic recombination events in Saccharomyces cerevisiae. Genetics 162, 603–614 (2002).
  CAS PubMed PubMed Central Google Scholar
• Jimeno, S., Rondon, A. G., Luna, R. & Aguilera, A. The yeast THO complex and mRNA export factors link RNA metabolism with transcription and genome instability. EMBO J. 21, 3526–3535 (2002).
  CAS PubMed PubMed Central Google Scholar
• Gaillard, H., Wellinger, R. E. & Aguilera, A. A new connection of mRNP biogenesis and export with transcription-coupled repair. Nucleic Acids Res. 35, 3893–3906 (2007).
  CAS PubMed PubMed Central Google Scholar
• García-Rubio, M. et al. Different physiological relevance of yeast THO/TREX subunits in gene expression and genome integrity. Mol. Genet. Genomics 279, 123–132 (2008).
  PubMed Google Scholar
• Schneider, M., Noegel, A. A. & Karakesisoglou, I. KASH-domain proteins and the cytoskeletal landscapes of the nuclear envelope. Biochem. Soc. Trans. 36, 1368–1372 (2008).
  CAS PubMed Google Scholar
• Kelly, S. M. & Corbett, A. H. Messenger RNA export from the nucleus: a series of molecular wardrobe changes. Traffic 10, 1199–1208 (2009).
  CAS PubMed PubMed Central Google Scholar
• Luna, R., Gaillard, H., Gonzalez-Aguilera, C. & Aguilera, A. Biogenesis of mRNPs: integrating different processes in the eukaryotic nucleus. Chromosoma 117, 319–331 (2008).
  CAS PubMed Google Scholar
• Hacker, S. & Krebber, H. Differential export requirements for shuttling serine/arginine-type mRNA-binding proteins. J. Biol. Chem. 279, 5049–5052 (2004).
  PubMed Google Scholar
• Iglesias, N. & Stutz, F. Regulation of mRNP dynamics along the export pathway. FEBS Lett. 582, 1987–1996 (2008).
  CAS PubMed Google Scholar