Open Access

Cell Research, volume 25, issue 3, pages 288-305

The Integrator complex controls the termination of transcription at diverse classes of gene targets

Skaar Jeffrey R ¹

Ferris Andrea L ²

Wu Xiaolin ³

Saraf Anita ⁴

Khanna Kum Kum ⁵

Florens Laurence ⁴

Washburn Michael P. ^{4, 6}

Hughes Stephen H ²

Pagano Michele ^{1, 7}

Hide authors affiliations Show authors affiliations: 7 affiliations

Department of Pathology, Laura and Isaac Perlmutter Cancer Center, New York University School of Medicine, New York, USA |

HIV Drug Resistance Program, National Cancer Institute, Frederick, USA |

Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, USA |

⁴

the Stowers Institute for Medical Research, Kansas City, USA |

⁵

QIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia |

⁶

Department of Pathology and Laboratory Medicine, the University of Kansas Medical Center, Kansas City, USA |

⁷

Howard Hughes Medical Institute, New York, USA |

Publication type: Journal Article

Publication date: 2015-02-13

Springer Nature

Journal: Cell Research

Quartile SCImago

Quartile WOS

Impact factor: 44.1

ISSN: 10010602, 17487838

DOI: 10.1038/cr.2015.19

Copy DOI

PubMed ID: 25675981

Molecular Biology

Cell Biology

Abstract

Complexes containing INTS3 and either NABP1 or NABP2 were initially characterized in DNA damage responses, but their biochemical function remained unknown. Using affinity purifications and HIV Integration targeting-sequencing (HIT-Seq), we find that these complexes are part of the Integrator complex, which binds RNA Polymerase II and regulates specific target genes. Integrator cleaves snRNAs as part of their processing to their mature form in a mechanism that is intimately coupled with transcription termination. However, HIT-Seq reveals that Integrator also binds to the 3′ end of replication-dependent histones and promoter proximal regions of genes with polyadenylated transcripts. Depletion of Integrator subunits results in transcription termination failure, disruption of histone mRNA processing, and polyadenylation of snRNAs and histone mRNAs. Furthermore, promoter proximal binding of Integrator negatively regulates expression of genes whose transcripts are normally polyadenylated. Integrator recruitment to all three gene classes is DSIF-dependent, suggesting that Integrator functions as a termination complex at DSIF-dependent RNA Polymerase II pause sites.

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Springer Nature	Springer Nature, 16, 15.09% Springer Nature 16 publications, 15.09%
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Proceedings of the National Academy of Sciences (PNAS)	Proceedings of the National Academy of Sciences (PNAS), 2, 1.89% Proceedings of the National Academy of Sciences (PNAS) 2 publications, 1.89%
eLife Sciences Publications	eLife Sciences Publications, 2, 1.89% eLife Sciences Publications 2 publications, 1.89%
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American Society for Biochemistry and Molecular Biology	American Society for Biochemistry and Molecular Biology, 1, 0.94% American Society for Biochemistry and Molecular Biology 1 publication, 0.94%
American Society of Hematology	American Society of Hematology, 1, 0.94% American Society of Hematology 1 publication, 0.94%
Genetics Society of America	Genetics Society of America, 1, 0.94% Genetics Society of America 1 publication, 0.94%
Dove Medical Press	Dove Medical Press, 1, 0.94% Dove Medical Press 1 publication, 0.94%
	5 10 15 20 25 30

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Skaar J. R. et al. The Integrator complex controls the termination of transcription at diverse classes of gene targets // Cell Research. 2015. Vol. 25. No. 3. pp. 288-305.

GOST all authors (up to 50) Copy

Skaar J. R., Ferris A. L., Wu X., Saraf A., Khanna K. K., Florens L., Washburn M. P., Hughes S. H., Pagano M. The Integrator complex controls the termination of transcription at diverse classes of gene targets // Cell Research. 2015. Vol. 25. No. 3. pp. 288-305.

RIS |

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RIS Copy

TY - JOUR

DO - 10.1038/cr.2015.19

UR - https://doi.org/10.1038%2Fcr.2015.19

TI - The Integrator complex controls the termination of transcription at diverse classes of gene targets

T2 - Cell Research

AU - Skaar, Jeffrey R

AU - Ferris, Andrea L

AU - Wu, Xiaolin

AU - Saraf, Anita

AU - Khanna, Kum Kum

AU - Florens, Laurence

AU - Washburn, Michael P.

AU - Hughes, Stephen H

AU - Pagano, Michele

PY - 2015

DA - 2015/02/13 00:00:00

PB - Springer Nature

SP - 288-305

IS - 3

VL - 25

PMID - 25675981

SN - 1001-0602

SN - 1748-7838

ER -

BibTex |

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BibTex Copy

@article{2015_Skaar,

author = {Jeffrey R Skaar and Andrea L Ferris and Xiaolin Wu and Anita Saraf and Kum Kum Khanna and Laurence Florens and Michael P. Washburn and Stephen H Hughes and Michele Pagano},

title = {The Integrator complex controls the termination of transcription at diverse classes of gene targets},

journal = {Cell Research},

year = {2015},

volume = {25},

publisher = {Springer Nature},

month = {feb},

url = {https://doi.org/10.1038%2Fcr.2015.19},

number = {3},

pages = {288--305},

doi = {10.1038/cr.2015.19}

}

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Skaar, Jeffrey R., et al. “The Integrator complex controls the termination of transcription at diverse classes of gene targets.” Cell Research, vol. 25, no. 3, Feb. 2015, pp. 288-305. https://doi.org/10.1038%2Fcr.2015.19.

Found error?

Publisher

Springer Nature

Journal

Cell Research

Quartile SCImago

Quartile WOS

Impact factor

44.1

ISSN

10010602 (Print)
17487838 (Electronic)