9g0a

Structural highlights

Function

SPT5H_HUMAN Component of the DRB sensitivity-inducing factor complex (DSIF complex), which regulates mRNA processing and transcription elongation by RNA polymerase II. DSIF positively regulates mRNA capping by stimulating the mRNA guanylyltransferase activity of RNGTT/CAP1A. DSIF also acts cooperatively with the negative elongation factor complex (NELF complex) to enhance transcriptional pausing at sites proximal to the promoter. Transcriptional pausing may facilitate the assembly of an elongation competent RNA polymerase II complex. DSIF and NELF promote pausing by inhibition of the transcription elongation factor TFIIS/S-II. TFIIS/S-II binds to RNA polymerase II at transcription pause sites and stimulates the weak intrinsic nuclease activity of the enzyme. Cleavage of blocked transcripts by RNA polymerase II promotes the resumption of transcription from the new 3' terminus and may allow repeated attempts at transcription through natural pause sites. DSIF can also positively regulate transcriptional elongation and is required for the efficient activation of transcriptional elongation by the HIV-1 nuclear transcriptional activator, Tat. DSIF acts to suppress transcriptional pausing in transcripts derived from the HIV-1 LTR and blocks premature release of HIV-1 transcripts at terminator sequences.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19]}

References

1. ↑ Wada T, Takagi T, Yamaguchi Y, Ferdous A, Imai T, Hirose S, Sugimoto S, Yano K, Hartzog GA, Winston F, Buratowski S, Handa H. DSIF, a novel transcription elongation factor that regulates RNA polymerase II processivity, is composed of human Spt4 and Spt5 homologs. Genes Dev. 1998 Feb 1;12(3):343-56. PMID:9450929
2. ↑ Wu-Baer F, Lane WS, Gaynor RB. Role of the human homolog of the yeast transcription factor SPT5 in HIV-1 Tat-activation. J Mol Biol. 1998 Mar 27;277(2):179-97. PMID:9514752 doi:S0022-2836(97)91601-6
3. ↑ Wada T, Takagi T, Yamaguchi Y, Watanabe D, Handa H. Evidence that P-TEFb alleviates the negative effect of DSIF on RNA polymerase II-dependent transcription in vitro. EMBO J. 1998 Dec 15;17(24):7395-403. PMID:9857195 doi:10.1093/emboj/17.24.7395
4. ↑ Yamaguchi Y, Takagi T, Wada T, Yano K, Furuya A, Sugimoto S, Hasegawa J, Handa H. NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase II elongation. Cell. 1999 Apr 2;97(1):41-51. PMID:10199401
5. ↑ Parada CA, Roeder RG. A novel RNA polymerase II-containing complex potentiates Tat-enhanced HIV-1 transcription. EMBO J. 1999 Jul 1;18(13):3688-701. PMID:10393184 doi:10.1093/emboj/18.13.3688
6. ↑ Wen Y, Shatkin AJ. Transcription elongation factor hSPT5 stimulates mRNA capping. Genes Dev. 1999 Jul 15;13(14):1774-9. PMID:10421630
7. ↑ Yamaguchi Y, Wada T, Watanabe D, Takagi T, Hasegawa J, Handa H. Structure and function of the human transcription elongation factor DSIF. J Biol Chem. 1999 Mar 19;274(12):8085-92. PMID:10075709
8. ↑ Kim JB, Yamaguchi Y, Wada T, Handa H, Sharp PA. Tat-SF1 protein associates with RAP30 and human SPT5 proteins. Mol Cell Biol. 1999 Sep;19(9):5960-8. PMID:10454543
9. ↑ Wada T, Orphanides G, Hasegawa J, Kim DK, Shima D, Yamaguchi Y, Fukuda A, Hisatake K, Oh S, Reinberg D, Handa H. FACT relieves DSIF/NELF-mediated inhibition of transcriptional elongation and reveals functional differences between P-TEFb and TFIIH. Mol Cell. 2000 Jun;5(6):1067-72. PMID:10912001
10. ↑ Ivanov D, Kwak YT, Guo J, Gaynor RB. Domains in the SPT5 protein that modulate its transcriptional regulatory properties. Mol Cell Biol. 2000 May;20(9):2970-83. PMID:10757782
11. ↑ Ping YH, Rana TM. DSIF and NELF interact with RNA polymerase II elongation complex and HIV-1 Tat stimulates P-TEFb-mediated phosphorylation of RNA polymerase II and DSIF during transcription elongation. J Biol Chem. 2001 Apr 20;276(16):12951-8. Epub 2000 Dec 8. PMID:11112772 doi:10.1074/jbc.M006130200
12. ↑ Renner DB, Yamaguchi Y, Wada T, Handa H, Price DH. A highly purified RNA polymerase II elongation control system. J Biol Chem. 2001 Nov 9;276(45):42601-9. Epub 2001 Sep 11. PMID:11553615 doi:10.1074/jbc.M104967200
13. ↑ Bourgeois CF, Kim YK, Churcher MJ, West MJ, Karn J. Spt5 cooperates with human immunodeficiency virus type 1 Tat by preventing premature RNA release at terminator sequences. Mol Cell Biol. 2002 Feb;22(4):1079-93. PMID:11809800
14. ↑ Kim DK, Inukai N, Yamada T, Furuya A, Sato H, Yamaguchi Y, Wada T, Handa H. Structure-function analysis of human Spt4: evidence that hSpt4 and hSpt5 exert their roles in transcriptional elongation as parts of the DSIF complex. Genes Cells. 2003 Apr;8(4):371-8. PMID:12653964
15. ↑ Kwak YT, Guo J, Prajapati S, Park KJ, Surabhi RM, Miller B, Gehrig P, Gaynor RB. Methylation of SPT5 regulates its interaction with RNA polymerase II and transcriptional elongation properties. Mol Cell. 2003 Apr;11(4):1055-66. PMID:12718890
16. ↑ Jennings BH, Shah S, Yamaguchi Y, Seki M, Phillips RG, Handa H, Ish-Horowicz D. Locus-specific requirements for Spt5 in transcriptional activation and repression in Drosophila. Curr Biol. 2004 Sep 21;14(18):1680-4. PMID:15380072 doi:10.1016/j.cub.2004.08.066
17. ↑ Fujinaga K, Irwin D, Huang Y, Taube R, Kurosu T, Peterlin BM. Dynamics of human immunodeficiency virus transcription: P-TEFb phosphorylates RD and dissociates negative effectors from the transactivation response element. Mol Cell Biol. 2004 Jan;24(2):787-95. PMID:14701750
18. ↑ Mandal SS, Chu C, Wada T, Handa H, Shatkin AJ, Reinberg D. Functional interactions of RNA-capping enzyme with factors that positively and negatively regulate promoter escape by RNA polymerase II. Proc Natl Acad Sci U S A. 2004 May 18;101(20):7572-7. Epub 2004 May 10. PMID:15136722 doi:10.1073/pnas.0401493101
19. ↑ Palangat M, Renner DB, Price DH, Landick R. A negative elongation factor for human RNA polymerase II inhibits the anti-arrest transcript-cleavage factor TFIIS. Proc Natl Acad Sci U S A. 2005 Oct 18;102(42):15036-41. Epub 2005 Oct 7. PMID:16214896 doi:10.1073/pnas.0409405102