Hyperosmotic stress alters the RNA polymerase II interactome and induces readthrough transcription despite widespread transcriptional repression.

Autor:	Rosa-Mercado NA; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06536, USA., Zimmer JT; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06536, USA., Apostolidi M; Department of Cellular and Molecular Physiology, Yale University, New Haven, CT 06510, USA; Systems Biology Institute, Yale University, West Haven, CT 06477, USA., Rinehart J; Department of Cellular and Molecular Physiology, Yale University, New Haven, CT 06510, USA; Systems Biology Institute, Yale University, West Haven, CT 06477, USA., Simon MD; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06536, USA., Steitz JA; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06536, USA; Howard Hughes Medical Institute, Yale University, New Haven, CT 06536, USA. Electronic address: joan.steitz@yale.edu.
Jazyk:	angličtina
Zdroj:	Molecular cell [Mol Cell] 2021 Feb 04; Vol. 81 (3), pp. 502-513.e4. Date of Electronic Publication: 2021 Jan 04.
DOI:	10.1016/j.molcel.2020.12.002
Abstrakt:	Stress-induced readthrough transcription results in the synthesis of downstream-of-gene (DoG)-containing transcripts. The mechanisms underlying DoG formation during cellular stress remain unknown. Nascent transcription profiles during DoG induction in human cell lines using TT-TimeLapse sequencing revealed widespread transcriptional repression upon hyperosmotic stress. Yet, DoGs are produced regardless of the transcriptional level of their upstream genes. ChIP sequencing confirmed that stress-induced redistribution of RNA polymerase (Pol) II correlates with the transcriptional output of genes. Stress-induced alterations in the Pol II interactome are observed by mass spectrometry. While certain cleavage and polyadenylation factors remain Pol II associated, Integrator complex subunits dissociate from Pol II under stress leading to a genome-wide loss of Integrator on DNA. Depleting the catalytic subunit of Integrator using siRNAs induces hundreds of readthrough transcripts, whose parental genes partially overlap those of stress-induced DoGs. Our results provide insights into the mechanisms underlying DoG production and how Integrator activity influences DoG transcription. Competing Interests: Declaration of interests J.A.S. is a member of the Molecular Cell Advisory Board. The authors have no further competing interests to declare. (Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu