MYC Recruits SPT5 to RNA Polymerase II to Promote Processive Transcription Elongation

被引：80

作者：

Baluapuri, Apoorva ^{[1
]}

Hofstetter, Julia ^{[1
]}

Stankovic, Nevenka Dudvarski ^{[1
]}

Endres, Theresa ^{[2
]}

Bhandare, Pranjali ^{[1
]}

Vos, Seychelle Monique ^{[3
]}

Adhikari, Bikash ^{[1
]}

Schwarz, Jessica Denise ^{[1
]}

Narain, Ashwin ^{[1
]}

Vogt, Markus ^{[1
]}

Wang, Shuang-Yan ^{[4
]}

Duester, Robert ^{[5
]}

Jung, Lisa Anna ^{[6
]}

Vanselow, Jens Thorsten ^{[4
]}

Wiegering, Armin ^{[2
,7
]}

Geyer, Matthias ^{[5
]}

Maric, Hans Michael ^{[4
]}

Gallant, Peter ^{[2
]}

Walz, Susanne ^{[8
]}

Schlosser, Andreas ^{[4
]}

Cramer, Patrick ^{[3
,6
]}

Eilers, Martin ^{[2
]}

Wolf, Elmar ^{[1
]}

机构：

[1] Univ Wurzburg, Canc Syst Biol Grp, Theodor Boveri Inst, D-97074 Wurzburg, Germany

[2] Univ Wurzburg, Dept Biochem & Mol Biol, Theodor Boveri Inst, D-97074 Wurzburg, Germany

[3] Max Planck Inst Biophys Chem, Dept Mol Biol, Fassberg 11, D-37077 Gottingen, Germany

[4] Rudolf Virchow Ctr Expt Biomed, Josef Schneider Str 2, D-97080 Wurzburg, Germany

[5] Univ Bonn, Inst Struct Biol, Sigmund Freud Str 25, D-53127 Bonn, Germany

[6] Karolinska Inst, Dept Biosci & Nutr, Halsovagen 7C, S-14157 Huddinge, Sweden

[7] Univ Hosp Wurzburg, Dept Gen Visceral Transplant Vasc & Pediat Surg, Josef Schneider Str 2, D-97080 Wurzburg, Germany

[8] Univ Wurzburg, Core Unit Bioinformat, Comprehens Canc Ctr Mainfranken, D-97074 Wurzburg, Germany

来源：

MOLECULAR CELL | 2019年 / 74卷 / 04期

基金：

欧洲研究理事会;

关键词：

C-MYC; GENE-EXPRESSION; COMPLEX; INITIATION; DYNAMICS; CANCER; ROLES; ACTIVATION; REVEALS; WIDE;

D O I：

10.1016/j.molcel.2019.02.031

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The MYC oncoprotein binds to promoter-proximal regions of virtually all transcribed genes and enhances RNA polymerase II (Pol II) function, but its precise mode of action is poorly understood. Using mass spectrometry of both MYC and Pol II complexes, we show here that MYC controls the assembly of Pol II with a small set of transcription elongation factors that includes SPT5, a subunit of the elongation factor DSIF. MYC directly binds SPT5, recruits SPT5 to promoters, and enables the CDK7-dependent transfer of SPT5 onto Pol II. Consistent with known functions of SPT5, MYC is required for fast and processive transcription elongation. Intriguingly, the high levels of MYC that are expressed in tumors sequester SPT5 into non-functional complexes, thereby decreasing the expression of growth-suppressive genes. Altogether, these results argue that MYC controls the productive assembly of processive Pol II elongation complexes and provide insight into how oncogenic levels of MYC permit uncontrolled cellular growth.

引用

页码：674 / +

页数：25

共 65 条

[1] Promoter-proximal pausing of RNA polymerase II: emerging roles in metazoans [J].

Adelman, Karen ;

Lis, John T. .

NATURE REVIEWS GENETICS, 2012, 13 (10) :720-731

[2] Characterization of molecular and cellular functions of the cyclin-dependent kinase CDK9 using a novel specific inhibitor [J].

Albert, T. K. ;

Rigault, C. ;

Eickhoff, J. ;

Baumgart, K. ;

Antrecht, C. ;

Klebl, B. ;

Mittler, G. ;

Meisterernst, M. .

BRITISH JOURNAL OF PHARMACOLOGY, 2014, 171 (01) :55-68

[3] Spt6 enhances the elongation rate of RNA polymerase II in vivo [J].

Ardehali, M. Behfar ;

Yao, Jie ;

Adelman, Karen ;

Fuda, Nicholas J. ;

Petesch, Steven J. ;

Webb, Watt W. ;

Lis, John T. .

EMBO JOURNAL, 2009, 28 (08) :1067-1077

[4] Structure of a transcribing RNA polymerase II-DSIF complex reveals a multidentate DNA-RNA clamp [J].

Bernecky, Carrie ;

Plitzko, Juergen M. ;

Cramer, Patrick .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2017, 24 (10) :809-+

[5] RNA polymerase II clustering through carboxy-terminal domain phase separation [J].

Boehning, Marc ;

Dugast-Darzacq, Claire ;

Rankovic, Marija ;

Hansen, Anders S. ;

Yu, Taekyung ;

Marie-Nelly, Herve ;

McSwiggen, David T. ;

Kokic, Goran ;

Dailey, Gina M. ;

Cramer, Patrick ;

Darzacq, Xavier ;

Zweckstetter, Markus .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2018, 25 (09) :833-+

[6] The MYC transcription factor network: balancing metabolism, proliferation and oncogenesis [J].

Carroll, Patrick A. ;

Freie, Brian W. ;

Mathsyaraja, Haritha ;

Eisenman, Robert N. .

FRONTIERS OF MEDICINE, 2018, 12 (04) :412-425

[7] Defining the Status of RNA Polymerase at Promoters [J].

Core, Leighton J. ;

Waterfall, Joshua J. ;

Gilchrist, Daniel A. ;

Fargo, David C. ;

Kwak, Hojoong ;

Adelman, Karen ;

Lis, John T. .

CELL REPORTS, 2012, 2 (04) :1025-1035

[8] MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification [J].

Cox, Juergen ;

Mann, Matthias .

NATURE BIOTECHNOLOGY, 2008, 26 (12) :1367-1372

[9] MYC on the Path to Cancer [J].

Dang, Chi V. .

CELL, 2012, 149 (01) :22-35

[10] Signaling Pathways Differentially Affect RNA Polymerase II Initiation, Pausing, and Elongation Rate in Cells [J].

Danko, Charles G. ;

Hah, Nasun ;

Luo, Xin ;

Martins, Andre L. ;

Core, Leighton ;

Lis, John T. ;

Siepel, Adam ;

Kraus, W. Lee .

MOLECULAR CELL, 2013, 50 (02) :212-222

← 1 2 3 4 5 6 7 →