Structure of activated transcription complex Pol II-DSIF-PAF-SPT6

被引：275

作者：

Vos, Seychelle M. ^{[1
]}

Farnung, Lucas ^{[1
]}

Boehning, Marc ^{[1
]}

Wigge, Christoph ^{[1
]}

Linden, Andreas ^{[2
,3
]}

Urlaub, Henning ^{[2
,3
]}

Cramer, Patrick ^{[1
]}

机构：

[1] Max Planck Inst Biophys Chem, Dept Mol Biol, Gottingen, Germany

[2] Max Planck Inst Biophys Chem, Bioanalyt Mass Spectrometry, Gottingen, Germany

[3] Univ Med Ctr Gottingen, Inst Clin Chem, Bioanalyt Grp, Gottingen, Germany

来源：

NATURE | 2018年 / 560卷 / 7720期

基金：

欧洲研究理事会;

关键词：

RNA-POLYMERASE-II; ELONGATION-FACTOR SPT6; PAF1; COMPLEX; P-TEFB; DNA HYBRID; CHROMATIN-STRUCTURE; CRYSTAL-STRUCTURE; SH2; DOMAIN; PROTEIN; PHOSPHORYLATION;

D O I：

10.1038/s41586-018-0440-4

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Gene regulation involves activation of RNA polymerase II (Pol II) that is paused and bound by the protein complexes DRB sensitivity-inducing factor (DSIF) and negative elongation factor (NELF). Here we show that formation of an activated Pol II elongation complex in vitro requires the kinase function of the positive transcription elongation factor b (P-TEFb) and the elongation factors PAF1 complex (PAF) and SPT6. The cryo-EM structure of an activated elongation complex of Sus scrofa Pol II and Honto sapiens DSIF, PAF and SPT6 was determined at 3.1 A resolution and compared to the structure of the paused elongation complex formed by Pol II, DSIF and NELF. PAF displaces NELF from the Pol II funnel for pause release. P-TEFb phosphorylates the Pol II linker to the C-terminal domain. SPT6 binds to the phosphorylated C-terminaldomain linker and opens the RNA clamp formed by DSIF. These results provide the molecular basis for Pol II pause release and elongation activation.

引用

页码：607 / +

页数：31

共 107 条

[81] A Tandem SH2 Domain in Transcription Elongation Factor Spt6 Binds the Phosphorylated RNA Polymerase II C-terminal Repeat Domain (CTD) [J].

Sun, Mai ;

Lariviere, Laurent ;

Dengl, Stefan ;

Mayer, Andreas ;

Cramer, Patrick .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (53) :41597-41603

[82]

SWANSON MS, 1992, GENETICS, V132, P325

[83] Structural Basis of Transcription: Mismatch-Specific Fidelity Mechanisms and Paused RNA Polymerase II with Frayed RNA [J].

Sydow, Jasmin F. ;

Brueckner, Florian ;

Cheung, Alan C. M. ;

Damsma, Gerke E. ;

Dengl, Stefan ;

Lehmann, Elisabeth ;

Vassylyev, Dmitry ;

Cramer, Patrick .

MOLECULAR CELL, 2009, 34 (06) :710-721

[84] Flexible fitting of atomic structures into electron microscopy maps using molecular dynamics [J].

Trabuco, Leonardo G. ;

Villa, Elizabeth ;

Mitra, Kakoli ;

Frank, Joachim ;

Schulten, Klaus .

STRUCTURE, 2008, 16 (05) :673-683

[85] NusG inhibits RNA polymerase backtracking by stabilizing the minimal transcription bubble [J].

Turtola, Matti ;

Belogurov, Georgiy A. .

ELIFE, 2016, 5

[86] Emerging Insights into the Roles of the Paf1 Complex in Gene Regulation [J].

Van Oss, S. Branden ;

Cucinotta, Christine E. ;

Arndt, Karen M. .

TRENDS IN BIOCHEMICAL SCIENCES, 2017, 42 (10) :788-798

[87] Structure of paused transcription complex Pol II-DSIF-NELF [J].

Vos, Seychelle M. ;

Farnung, Lucas ;

Urlaub, Henning ;

Cramer, Patrick .

NATURE, 2018, 560 (7720) :601-+

[88] Architecture and RNA binding of the human negative elongation factor [J].

Vos, Seychelle M. ;

Poellmann, David ;

Caizzi, Livia ;

Hofmann, Katharina B. ;

Rombaut, Pascaline ;

Zimniak, Tomasz ;

Herzog, Franz ;

Cramer, Patrick .

ELIFE, 2016, 5

[89] FACT relieves DSIF/NELF-mediated inhibition of transcriptional elongation and reveals functional differences between P-TEFb and TFIIH [J].

Wada, T ;

Orphanides, G ;

Hasegawa, J ;

Kim, DK ;

Shima, D ;

Yamaguchi, Y ;

Fukuda, A ;

Hisatake, K ;

Oh, S ;

Reinberg, D ;

Handa, H .

MOLECULAR CELL, 2000, 5 (06) :1067-1072

[90] DSIF, a novel transcription elongation factor that regulates RNA polymerase II processivity, is composed of human Spt4 and Spt5 homologs [J].

Wada, T ;

Takagi, T ;

Yamaguchi, Y ;

Ferdous, A ;

Imai, T ;

Hirose, S ;

Sugimoto, S ;

Yano, K ;

Hartzog, GA ;

Winston, F ;

Buratowski, S ;

Handa, H .

GENES & DEVELOPMENT, 1998, 12 (03) :343-356

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