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

[51] Overextended RNA:DNA hybrid as a negative regulator of RNA polymerase II processivity [J].

Kireeva, ML ;

Komissarova, N ;

Kashlev, M .

JOURNAL OF MOLECULAR BIOLOGY, 2000, 299 (02) :325-335

[52] RNA-DNA and DNA-DNA base-pairing at the upstream edge of the transcription bubble regulate translocation of RNA polymerase and transcription rate [J].

Klreeva, Maria ;

Trang, Cyndi ;

Matevosyan, Gayane ;

Turek-Herman, Joshua ;

Chasov, Vitaly ;

Lubkowska, Lucyna ;

Kashlev, Mikhail .

NUCLEIC ACIDS RESEARCH, 2018, 46 (11) :5764-5775

[53]

Komissarova N, 2003, METHOD ENZYMOL, V371, P233

[54] Xlink Analyzer: Software for analysis and visualization of cross-linking data in the context of three-dimensional structures [J].

Kosinski, Jan ;

von Appen, Alexander ;

Ori, Alessandro ;

Karius, Kai ;

Mueller, Christoph W. ;

Beck, Martin .

JOURNAL OF STRUCTURAL BIOLOGY, 2015, 189 (03) :177-183

[55] RNA polymerase II elongation factors of Saccharomyces cerevisiae:: a targeted proteomnics approach [J].

Krogan, NJ ;

Kim, M ;

Ahn, SH ;

Zhong, GQ ;

Kobor, MS ;

Cagney, G ;

Emili, A ;

Shilatifard, A ;

Buratowski, S ;

Greenblatt, JF .

MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (20) :6979-6992

[56] A pause sequence enriched at translation start sites drives transcription dynamics in vivo [J].

Larson, Matthew H. ;

Mooney, Rachel A. ;

Peters, Jason M. ;

Windgassen, Tricia ;

Nayak, Dhananjaya ;

Gross, Carol A. ;

Block, Steven M. ;

Greenleaf, William J. ;

Landick, Robert ;

Weissman, Jonathan S. .

SCIENCE, 2014, 344 (6187) :1042-1047

[57] Phosphorylation of the Transcription Elongation Factor Spt5 by Yeast Bur1 Kinase Stimulates Recruitment of the PAF Complex [J].

Liu, Ying ;

Warfield, Linda ;

Zhang, Chao ;

Luo, Jie ;

Allen, Jasmina ;

Lang, Walter H. ;

Ranish, Jeffrey ;

Shokat, Kevan M. ;

Hahn, Steven .

MOLECULAR AND CELLULAR BIOLOGY, 2009, 29 (17) :4852-4863

[58] Multiple P-TEFbs cooperatively regulate the release of promoter-proximally paused RNA polymerase II [J].

Lu, Xiaodong ;

Zhu, Xinxing ;

Li, You ;

Liu, Min ;

Yu, Bin ;

Wang, Yu ;

Rao, Muhua ;

Yang, Haiyang ;

Zhou, Kai ;

Wang, Yao ;

Chen, Yanheng ;

Chen, Meihua ;

Zhuang, Songkuan ;

Chen, Lin-Feng ;

Liu, Runzhong ;

Chen, Ruichuan .

NUCLEIC ACIDS RESEARCH, 2016, 44 (14) :6853-6867

[59] PURIFICATION OF P-TEFB, A TRANSCRIPTION FACTOR REQUIRED FOR THE TRANSITION INTO PRODUCTIVE ELONGATION [J].

MARSHALL, NF ;

PRICE, DH .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (21) :12335-12338

[60] Control of RNA polymerase II elongation potential by a novel carboxyl-terminal domain kinase [J].

Marshall, NF ;

Peng, JM ;

Xie, Z ;

Price, DH .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (43) :27176-27183

← 1 2 3 4 5 6 7 8 9 10 →