Open Access

Science, volume 374, issue 6569, pages 883-887

Structural basis of Integrator-mediated transcription regulation

Fianu Isaac ¹

Chen Ying ¹

Dienemann Christian ¹

Dybkov Olexandr ²

Linden Andreas ^{3, 4}

Urlaub Henning ^{3, 4}

Cramer Patrick ¹

Hide authors affiliations Show authors affiliations: 4 affiliations

Department of Molecular Biology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany. |

Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany. |

Bioanalytical Mass Spectrometry, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany. |

⁴

Institute of Clinical Chemistry, Bioanalytics Group, University Medical Center Göttingen, 37075 Göttingen, Germany. |

Publication type: Journal Article

Publication date: 2021-11-12

American Association for the Advancement of Science (AAAS)

Journal: Science

Quartile SCImago

Quartile WOS

Impact factor: 56.9

ISSN: 00368075, 10959203

DOI: 10.1126/science.abk0154

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Multidisciplinary

Abstract

Description How Integrator ends transcription early Transcription is the central process that activates the genetic information in cells, but our understanding of how gene transcription is regulated is incomplete. The so-called Integrator can stop the transcribing enzyme RNA polymerase II at the beginning of genes, but how such downregulation of transcription occurs is unclear. Fianu et al. present the three-dimensional structure of Integrator bound to the transcribing polymerase complex, providing molecular and mechanistic insights into how Integrator mediates transcription regulation. —DJ Structural analysis suggests how Integrator-PP2A counteracts Pol II elongation and mediates nascent RNA cleavage and transcription termination. Integrator and protein phosphatase 2A (PP2A) form a complex that dephosphorylates paused RNA polymerase II (Pol II), cleaves the nascent RNA, and terminates transcription. We report the structure of the pretermination complex containing the human Integrator-PP2A complex bound to paused Pol II. Integrator binds Pol II and the pausing factors DSIF and NELF to exclude binding of the elongation factors SPT6 and PAF1 complex. Integrator also binds the C-terminal domain of Pol II and positions PP2A to counteract Pol II phosphorylation and elongation. The Integrator endonuclease docks to the RNA exit site and opens to cleave nascent RNA about 20 nucleotides from the Pol II active site. Integrator does not bind the DNA clamps formed by Pol II and DSIF, enabling release of DNA and transcription termination.

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Citations by journals

	2 4 6 8 10 12
Molecular Cell	Molecular Cell, 11, 14.29% Molecular Cell 11 publications, 14.29%
Current Opinion in Structural Biology	Current Opinion in Structural Biology, 4, 5.19% Current Opinion in Structural Biology 4 publications, 5.19%
Nature Reviews Molecular Cell Biology	Nature Reviews Molecular Cell Biology, 3, 3.9% Nature Reviews Molecular Cell Biology 3 publications, 3.9%
Cell Reports	Cell Reports, 3, 3.9% Cell Reports 3 publications, 3.9%
Science advances	Science advances, 3, 3.9% Science advances 3 publications, 3.9%
Computational and Structural Biotechnology Journal	Computational and Structural Biotechnology Journal, 2, 2.6% Computational and Structural Biotechnology Journal 2 publications, 2.6%
Cell	Cell, 2, 2.6% Cell 2 publications, 2.6%
Nucleic Acids Research	Nucleic Acids Research, 2, 2.6% Nucleic Acids Research 2 publications, 2.6%
Biomedicines	Biomedicines, 1, 1.3% Biomedicines 1 publication, 1.3%
Journal of Cell Science	Journal of Cell Science, 1, 1.3% Journal of Cell Science 1 publication, 1.3%
Biochemical Society Transactions	Biochemical Society Transactions, 1, 1.3% Biochemical Society Transactions 1 publication, 1.3%
Nature Communications	Nature Communications, 1, 1.3% Nature Communications 1 publication, 1.3%
Wiley interdisciplinary reviews. RNA	Wiley interdisciplinary reviews. RNA, 1, 1.3% Wiley interdisciplinary reviews. RNA 1 publication, 1.3%
iScience	iScience, 1, 1.3% iScience 1 publication, 1.3%
American Journal of Human Genetics	American Journal of Human Genetics, 1, 1.3% American Journal of Human Genetics 1 publication, 1.3%
PLoS Pathogens	PLoS Pathogens, 1, 1.3% PLoS Pathogens 1 publication, 1.3%
Protein and Cell	Protein and Cell, 1, 1.3% Protein and Cell 1 publication, 1.3%
Transcription	Transcription, 1, 1.3% Transcription 1 publication, 1.3%
eLife	eLife, 1, 1.3% eLife 1 publication, 1.3%
Genes and Development	Genes and Development, 1, 1.3% Genes and Development 1 publication, 1.3%
EMBO Reports	EMBO Reports, 1, 1.3% EMBO Reports 1 publication, 1.3%
Annual Review of Biochemistry	Annual Review of Biochemistry, 1, 1.3% Annual Review of Biochemistry 1 publication, 1.3%
Trends in Cancer	Trends in Cancer, 1, 1.3% Trends in Cancer 1 publication, 1.3%
Biochemical and Biophysical Research Communications	Biochemical and Biophysical Research Communications, 1, 1.3% Biochemical and Biophysical Research Communications 1 publication, 1.3%
NAR Genomics and Bioinformatics	NAR Genomics and Bioinformatics, 1, 1.3% NAR Genomics and Bioinformatics 1 publication, 1.3%
Medicina	Medicina, 1, 1.3% Medicina 1 publication, 1.3%
ACS Pharmacology & Translational Science	ACS Pharmacology & Translational Science, 1, 1.3% ACS Pharmacology & Translational Science 1 publication, 1.3%
Plant Cell	Plant Cell, 1, 1.3% Plant Cell 1 publication, 1.3%
Nature Structural and Molecular Biology	Nature Structural and Molecular Biology, 1, 1.3% Nature Structural and Molecular Biology 1 publication, 1.3%
	2 4 6 8 10 12

Citations by publishers

	5 10 15 20 25 30
Elsevier	Elsevier, 26, 33.77% Elsevier 26 publications, 33.77%
Springer Nature	Springer Nature, 6, 7.79% Springer Nature 6 publications, 7.79%
American Association for the Advancement of Science (AAAS)	American Association for the Advancement of Science (AAAS), 3, 3.9% American Association for the Advancement of Science (AAAS) 3 publications, 3.9%
Oxford University Press	Oxford University Press, 3, 3.9% Oxford University Press 3 publications, 3.9%
Multidisciplinary Digital Publishing Institute (MDPI)	Multidisciplinary Digital Publishing Institute (MDPI), 2, 2.6% Multidisciplinary Digital Publishing Institute (MDPI) 2 publications, 2.6%
Taylor & Francis	Taylor & Francis, 2, 2.6% Taylor & Francis 2 publications, 2.6%
The Company of Biologists	The Company of Biologists, 1, 1.3% The Company of Biologists 1 publication, 1.3%
Portland Press	Portland Press, 1, 1.3% Portland Press 1 publication, 1.3%
Wiley	Wiley, 1, 1.3% Wiley 1 publication, 1.3%
Public Library of Science (PLoS)	Public Library of Science (PLoS), 1, 1.3% Public Library of Science (PLoS) 1 publication, 1.3%
eLife Sciences Publications	eLife Sciences Publications, 1, 1.3% eLife Sciences Publications 1 publication, 1.3%
Cold Spring Harbor Laboratory	Cold Spring Harbor Laboratory, 1, 1.3% Cold Spring Harbor Laboratory 1 publication, 1.3%
EMBO press	EMBO press, 1, 1.3% EMBO press 1 publication, 1.3%
Annual Reviews	Annual Reviews, 1, 1.3% Annual Reviews 1 publication, 1.3%
American Chemical Society (ACS)	American Chemical Society (ACS), 1, 1.3% American Chemical Society (ACS) 1 publication, 1.3%
American Society of Plant Biologists	American Society of Plant Biologists, 1, 1.3% American Society of Plant Biologists 1 publication, 1.3%
The Royal Society	The Royal Society, 1, 1.3% The Royal Society 1 publication, 1.3%
	5 10 15 20 25 30

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Fianu I. et al. Structural basis of Integrator-mediated transcription regulation // Science. 2021. Vol. 374. No. 6569. pp. 883-887.

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Fianu I., Chen Y., Dienemann C., Dybkov O., Linden A., Urlaub H., Cramer P. Structural basis of Integrator-mediated transcription regulation // Science. 2021. Vol. 374. No. 6569. pp. 883-887.

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RIS Copy

TY - JOUR

DO - 10.1126/science.abk0154

UR - https://doi.org/10.1126%2Fscience.abk0154

TI - Structural basis of Integrator-mediated transcription regulation

T2 - Science

AU - Fianu, Isaac

AU - Chen, Ying

AU - Dienemann, Christian

AU - Dybkov, Olexandr

AU - Linden, Andreas

AU - Urlaub, Henning

AU - Cramer, Patrick

PY - 2021

DA - 2021/11/12 00:00:00

PB - American Association for the Advancement of Science (AAAS)

SP - 883-887

IS - 6569

VL - 374

SN - 0036-8075

SN - 1095-9203

ER -

BibTex |

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@article{2021_Fianu,

author = {Isaac Fianu and Ying Chen and Christian Dienemann and Olexandr Dybkov and Andreas Linden and Henning Urlaub and Patrick Cramer},

title = {Structural basis of Integrator-mediated transcription regulation},

journal = {Science},

year = {2021},

volume = {374},

publisher = {American Association for the Advancement of Science (AAAS)},

month = {nov},

url = {https://doi.org/10.1126%2Fscience.abk0154},

number = {6569},

pages = {883--887},

doi = {10.1126/science.abk0154}

}

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Fianu, Isaac, et al. “Structural basis of Integrator-mediated transcription regulation.” Science, vol. 374, no. 6569, Nov. 2021, pp. 883-887. https://doi.org/10.1126%2Fscience.abk0154.

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Publisher

American Association for the Advancement of Science (AAAS)

Journal

Science

Quartile SCImago

Quartile WOS

Impact factor

56.9

ISSN

00368075 (Print)
10959203 (Electronic)