| Structural highlights
Function
[NUP1_YEAST] Functions as a component of the nuclear pore complex (NPC). NPC components, collectively referred to as nucleoporins (NUPs), can play the role of both NPC structural components and of docking or interaction partners for transiently associated nuclear transport factors. Active directional transport is assured by both, a Phe-Gly (FG) repeat affinity gradient for these transport factors across the NPC and a transport cofactor concentration gradient across the nuclear envelope (GSP1 and GSP2 GTPases associated predominantly with GTP in the nucleus, with GDP in the cytoplasm). As one of the FG repeat nucleoporins NUP1 is involved in interactions with and guidance of nuclear transport receptors such as SRP1-KAP95 (importin alpha and beta) through the NPC. Like the closely related NUP2 it also plays an important role in disassembling and recycling SRP1-KAP95 to the cytoplasm after nuclear import. Upon entry of the heterotrimeric SRP1-KAP95-cargo complex in the nucleus, NUP1 binds through its C-terminus to KAP95, thus accelerating the release of KAP95 and, indirectly, of the nuclear localization signal (NLS)-containing cargo from the SRP1-KAP95-cargo complex.[1] [2] [3] [4] [5] [6] [7] [8] [9] [CDC31_YEAST] Functions as a component of the nuclear pore complex (NPC) and the spindle pole body (SPB) half-bridge. At the SPB, it is recruited by KAR1 and MPS3 to the SPB half-bridge and involved in the initial steps of SPB duplication. It probably plays a similar role in de novo assembly of NPCs at the nuclear envelope. Also involved in connection with the protein kinase KIC1 in the maintenance of cell morphology and integrity.[10] [11] [12] [13] [14] [15] [SUS1_YEAST] Involved in mRNA export coupled transcription activation by association with both the TREX-2 and the SAGA complexes. The transcription regulatory histone acetylation (HAT) complex SAGA is involved in RNA polymerase II-dependent regulation of approximately 10% of yeast genes. At the promoters, SAGA is required for recruitment of the basal transcription machinery. It influences RNA polymerase II transcriptional activity through different activities such as TBP interaction (SPT3, SPT8 and SPT20) and promoter selectivity, interaction with transcription activators (GCN5, ADA2, ADA3 and TRA1), and chromatin modification through histone acetylation (GCN5) and deubiquitination (UBP8). SUS1 forms a distinct functional SAGA module with UBP8, SGF11 and SGF73 required for deubiquitination of H2B and for the maintenance of steady-state H3 methylation levels. The TREX-2 complex 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. TREX-2 participates in mRNA export and accurate chromatin positioning in the nucleus by tethering genes to the nuclear periphery. SUS1 has also a role in mRNP biogenesis and maintenance of genome integrity through preventing RNA-mediated genome instability. Finally SUS1 has a role in response to DNA damage induced by methyl methane sulfonate (MMS) and replication arrest induced by hydroxyurea.[16] [17] [18] [19] [20] [21] [22] [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.[23] [24]
Publication Abstract from PubMed
The conserved Sac3:Thp1:Sem1:Sus1:Cdc31 (TREX2) complex binds to nuclear pore complexes (NPCs) and, in addition to integrating mRNA nuclear export with preceding steps in the gene expression pathway, facilitates re-positioning of highly regulated actively transcribing genes (such as GAL1) to NPCs. Although TREX2 is thought to bind NPC protein Nup1, defining the precise role of this interaction has been frustrated by the complex pleiotropic phenotype exhibited by nup1Delta strains. To provide a structural framework for understanding the binding of TREX2 to NPCs and its function in the gene expression pathway, we have determined the structure of the Nup1:TREX2 interaction interface and used this information to engineer a Sac3 variant that impairs NPC binding while not compromising TREX2 assembly. This variant inhibited the NPC association of both de-repressed and activated GAL1 and also produced mRNA export and growth defects. These results indicate that the TREX2:Nup1 interaction facilitates the efficient nuclear export of bulk mRNA together with the re-positioning of GAL1 to NPCs that is required for transcriptional control that is mediated by removal of SUMO from repressors by NPC-bound Ulp1.
Structural basis for binding the TREX2 complex to nuclear pores, GAL1 localisation and mRNA export.,Jani D, Valkov E, Stewart M Nucleic Acids Res. 2014 Apr 4. PMID:24705649[25]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Solsbacher J, Maurer P, Vogel F, Schlenstedt G. Nup2p, a yeast nucleoporin, functions in bidirectional transport of importin alpha. Mol Cell Biol. 2000 Nov;20(22):8468-79. PMID:11046143
- ↑ Allen NP, Huang L, Burlingame A, Rexach M. Proteomic analysis of nucleoporin interacting proteins. J Biol Chem. 2001 Aug 3;276(31):29268-74. Epub 2001 May 31. PMID:11387327 doi:http://dx.doi.org/10.1074/jbc.M102629200
- ↑ Denning D, Mykytka B, Allen NP, Huang L, Al Burlingame, Rexach M. The nucleoporin Nup60p functions as a Gsp1p-GTP-sensitive tether for Nup2p at the nuclear pore complex. J Cell Biol. 2001 Sep 3;154(5):937-50. PMID:11535617 doi:http://dx.doi.org/10.1083/jcb.200101007
- ↑ Bayliss R, Littlewood T, Strawn LA, Wente SR, Stewart M. GLFG and FxFG nucleoporins bind to overlapping sites on importin-beta. J Biol Chem. 2002 Dec 27;277(52):50597-606. Epub 2002 Oct 7. PMID:12372823 doi:10.1074/jbc.M209037200
- ↑ Allen NP, Patel SS, Huang L, Chalkley RJ, Burlingame A, Lutzmann M, Hurt EC, Rexach M. Deciphering networks of protein interactions at the nuclear pore complex. Mol Cell Proteomics. 2002 Dec;1(12):930-46. PMID:12543930
- ↑ Gilchrist D, Mykytka B, Rexach M. Accelerating the rate of disassembly of karyopherin.cargo complexes. J Biol Chem. 2002 May 17;277(20):18161-72. Epub 2002 Feb 26. PMID:11867631 doi:http://dx.doi.org/10.1074/jbc.M112306200
- ↑ Pyhtila B, Rexach M. A gradient of affinity for the karyopherin Kap95p along the yeast nuclear pore complex. J Biol Chem. 2003 Oct 24;278(43):42699-709. Epub 2003 Aug 12. PMID:12917401 doi:http://dx.doi.org/10.1074/jbc.M307135200
- ↑ Denning DP, Patel SS, Uversky V, Fink AL, Rexach M. Disorder in the nuclear pore complex: the FG repeat regions of nucleoporins are natively unfolded. Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2450-5. Epub 2003 Feb 25. PMID:12604785 doi:10.1073/pnas.0437902100
- ↑ Strawn LA, Shen T, Shulga N, Goldfarb DS, Wente SR. Minimal nuclear pore complexes define FG repeat domains essential for transport. Nat Cell Biol. 2004 Mar;6(3):197-206. Epub 2004 Feb 22. PMID:15039779 doi:10.1038/ncb1097
- ↑ Biggins S, Rose MD. Direct interaction between yeast spindle pole body components: Kar1p is required for Cdc31p localization to the spindle pole body. J Cell Biol. 1994 May;125(4):843-52. PMID:8188750
- ↑ Vallen EA, Ho W, Winey M, Rose MD. Genetic interactions between CDC31 and KAR1, two genes required for duplication of the microtubule organizing center in Saccharomyces cerevisiae. Genetics. 1994 Jun;137(2):407-22. PMID:8070654
- ↑ Sullivan DS, Biggins S, Rose MD. The yeast centrin, cdc31p, and the interacting protein kinase, Kic1p, are required for cell integrity. J Cell Biol. 1998 Nov 2;143(3):751-65. PMID:9813095
- ↑ Ivanovska I, Rose MD. Fine structure analysis of the yeast centrin, Cdc31p, identifies residues specific for cell morphology and spindle pole body duplication. Genetics. 2001 Feb;157(2):503-18. PMID:11156974
- ↑ Jaspersen SL, Giddings TH Jr, Winey M. Mps3p is a novel component of the yeast spindle pole body that interacts with the yeast centrin homologue Cdc31p. J Cell Biol. 2002 Dec 23;159(6):945-56. Epub 2002 Dec 16. PMID:12486115 doi:http://dx.doi.org/10.1083/jcb.200208169
- ↑ Kilmartin JV. Sfi1p has conserved centrin-binding sites and an essential function in budding yeast spindle pole body duplication. J Cell Biol. 2003 Sep 29;162(7):1211-21. Epub 2003 Sep 22. PMID:14504268 doi:http://dx.doi.org/10.1083/jcb.200307064
- ↑ Fischer T, Rodriguez-Navarro S, Pereira G, Racz A, Schiebel E, Hurt E. Yeast centrin Cdc31 is linked to the nuclear mRNA export machinery. Nat Cell Biol. 2004 Sep;6(9):840-8. Epub 2004 Aug 15. PMID:15311284 doi:10.1038/ncb1163
- ↑ Kastenmayer JP, Ni L, Chu A, Kitchen LE, Au WC, Yang H, Carter CD, Wheeler D, Davis RW, Boeke JD, Snyder MA, Basrai MA. Functional genomics of genes with small open reading frames (sORFs) in S. cerevisiae. Genome Res. 2006 Mar;16(3):365-73. PMID:16510898 doi:16/3/365
- ↑ Kohler A, Pascual-Garcia P, Llopis A, Zapater M, Posas F, Hurt E, Rodriguez-Navarro S. The mRNA export factor Sus1 is involved in Spt/Ada/Gcn5 acetyltransferase-mediated H2B deubiquitinylation through its interaction with Ubp8 and Sgf11. Mol Biol Cell. 2006 Oct;17(10):4228-36. Epub 2006 Jul 19. PMID:16855026 doi:E06-02-0098
- ↑ Cabal GG, Genovesio A, Rodriguez-Navarro S, Zimmer C, Gadal O, Lesne A, Buc H, Feuerbach-Fournier F, Olivo-Marin JC, Hurt EC, Nehrbass U. SAGA interacting factors confine sub-diffusion of transcribed genes to the nuclear envelope. Nature. 2006 Jun 8;441(7094):770-3. PMID:16760982 doi:10.1038/nature04752
- ↑ Pascual-Garcia P, Govind CK, Queralt E, Cuenca-Bono B, Llopis A, Chavez S, Hinnebusch AG, Rodriguez-Navarro S. Sus1 is recruited to coding regions and functions during transcription elongation in association with SAGA and TREX2. Genes Dev. 2008 Oct 15;22(20):2811-22. doi: 10.1101/gad.483308. PMID:18923079 doi:10.1101/gad.483308
- ↑ Gonzalez-Aguilera C, Tous C, Gomez-Gonzalez B, Huertas P, Luna R, Aguilera A. The THP1-SAC3-SUS1-CDC31 complex works in transcription elongation-mRNA export preventing RNA-mediated genome instability. Mol Biol Cell. 2008 Oct;19(10):4310-8. doi: 10.1091/mbc.E08-04-0355. Epub 2008, Jul 30. PMID:18667528 doi:10.1091/mbc.E08-04-0355
- ↑ Chekanova JA, Abruzzi KC, Rosbash M, Belostotsky DA. Sus1, Sac3, and Thp1 mediate post-transcriptional tethering of active genes to the nuclear rim as well as to non-nascent mRNP. RNA. 2008 Jan;14(1):66-77. Epub 2007 Nov 14. PMID:18003937 doi:10.1261/rna.764108
- ↑ 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
- ↑ Jani D, Valkov E, Stewart M. Structural basis for binding the TREX2 complex to nuclear pores, GAL1 localisation and mRNA export. Nucleic Acids Res. 2014 Apr 4. PMID:24705649 doi:http://dx.doi.org/10.1093/nar/gku252
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