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Structural basis for binding the TREX2 complex to nuclear pores, GAL1 localisation and mRNA export.

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Jani D, Valkov E, Stewart M
OpenAccess logo Nucleic Acids Res 42 6686-97 (2014)
Cited: 45 times
EuropePMC logo PMID: 24705649

Abstract

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 nup1Δ 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.

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  2. Structural basis for binding the TREX2 complex to nuclear pores, GAL1 localisation and mRNA export. Jani D, Valkov E, Stewart M. Nucleic Acids Res 42 6686-6697 (2014)
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  2. The Structure of the Nuclear Pore Complex (An Update). Lin DH, Hoelz A. Annu Rev Biochem 88 725-783 (2019)
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  10. Dynamic modules of the coactivator SAGA in eukaryotic transcription. Cheon Y, Kim H, Park K, Kim M, Lee D. Exp Mol Med 52 991-1003 (2020)
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  13. The Nuclear Pore Complex as a Transcription Regulator. Sumner MC, Brickner J. Cold Spring Harb Perspect Biol 14 a039438 (2022)
  14. Strength in Diversity: Nuclear Export of Viral RNAs. Gales JP, Kubina J, Geldreich A, Dimitrova M. Viruses 12 E1014 (2020)
  15. Nuclear mRNA maturation and mRNA export control: from trypanosomes to opisthokonts. Kramer S. Parasitology 148 1196-1218 (2021)
  16. The Great Escape: mRNA Export through the Nuclear Pore Complex. De Magistris P. Int J Mol Sci 22 11767 (2021)
  17. Nuclear mRNA Export and Aging. Park HS, Lee J, Lee HS, Ahn SH, Ryu HY. Int J Mol Sci 23 5451 (2022)
  18. mRNA export in the apicomplexan parasite Toxoplasma gondii: emerging divergent components of a crucial pathway. Ávila AR, Cabezas-Cruz A, Gissot M. Parasit Vectors 11 62 (2018)
  19. Evolution and diversification of the nuclear pore complex. Makarov AA, Padilla-Mejia NE, Field MC. Biochem Soc Trans 49 1601-1619 (2021)
  20. Structural Basis for the Functional Diversity of Centrins: A Focus on Calcium Sensing Properties and Target Recognition. Pedretti M, Bombardi L, Conter C, Favretto F, Dominici P, Astegno A. Int J Mol Sci 22 12173 (2021)

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