4wa6

Structural highlights

Function

[SGF73_YEAST] Functions as component of the transcription regulatory histone acetylation (HAT) complex SAGA. SAGA is involved in RNA polymerase II-dependent transcriptional 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). SAGA acetylates nucleosomal histone H3 to some extent (to form H3K9ac, H3K14ac, H3K18ac and H3K23ac). SAGA interacts with DNA via upstream activating sequences (UASs). [UBP8_YEAST] Functions as histone deubiquitinating component of the transcription regulatory histone acetylation (HAT) complexes SAGA and SLIK. SAGA is involved in RNA polymerase II-dependent transcriptional 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). SAGA acetylates nucleosomal histone H3 to some extent (to form H3K9ac, H3K14ac, H3K18ac and H3K23ac). SAGA interacts with DNA via upstream activating sequences (UASs). SLIK is proposed to have partly overlapping functions with SAGA. It preferentially acetylates methylated histone H3, at least after activation at the GAL1-10 locus. Together with SGF11, is required for histone H2B deubiquitination.^{[1] [2] [3]} [SGF11_YEAS7] Functions as component of the transcription regulatory histone acetylation (HAT) complex SAGA. 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 and promoter selectivity, interaction with transcription activators, and chromatin modification through histone acetylation and deubiquitination. SAGA acetylates nucleosomal histone H3 to some extent (to form H3K9ac, H3K14ac, H3K18ac and H3K23ac). SAGA interacts with DNA via upstream activating sequences (UASs). Involved in transcriptional regulation of a subset of SAGA-regulated genes. Within the SAGA complex, participates in a subcomplex, that specifically deubiquitinates histones H2B. [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.^{[4] [5] [6] [7] [8] [9] [10]}

References

1. ↑ Grant PA, Eberharter A, John S, Cook RG, Turner BM, Workman JL. Expanded lysine acetylation specificity of Gcn5 in native complexes. J Biol Chem. 1999 Feb 26;274(9):5895-900. PMID:10026213
2. ↑ Daniel JA, Torok MS, Sun ZW, Schieltz D, Allis CD, Yates JR 3rd, Grant PA. Deubiquitination of histone H2B by a yeast acetyltransferase complex regulates transcription. J Biol Chem. 2004 Jan 16;279(3):1867-71. Epub 2003 Dec 3. PMID:14660634 doi:10.1074/jbc.C300494200
3. ↑ Ingvarsdottir K, Krogan NJ, Emre NC, Wyce A, Thompson NJ, Emili A, Hughes TR, Greenblatt JF, Berger SL. H2B ubiquitin protease Ubp8 and Sgf11 constitute a discrete functional module within the Saccharomyces cerevisiae SAGA complex. Mol Cell Biol. 2005 Feb;25(3):1162-72. PMID:15657441 doi:25/3/1162
4. ↑ 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
5. ↑ 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
6. ↑ 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
7. ↑ 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
8. ↑ 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
9. ↑ 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
10. ↑ 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