The CTD Is Not Essential for the Post-Initiation Control of RNA Polymerase II Activity

Alan Gerber; Robert G. Roeder

doi:10.1016/j.jmb.2020.07.010

The CTD Is Not Essential for the Post-Initiation Control of RNA Polymerase II Activity

Alan Gerber, Robert G. Roeder

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Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Interest in the C-terminal domain (CTD) of the RPB1 subunit of the RNA polymerase II (Pol II) has been revived in recent years, owing to its numerous posttranslational modifications and its “phase-separation” properties. A large number of studies have shown that the status of CTD modifications is associated with the activity of Pol II during the transcription cycle. However, because this domain is essential in living cells, the functional requirement of the full CTD for the control of Pol II activity at endogenous mammalian genes has never been addressed directly in living cells. Using an inducible Pol II-degradation system that we previously established, we investigated here the roles of the CTD in the post-initiation control of Pol II. The selective ablation of the RPB1 CTD, post-initiation, at promoter-proximal pause-sites revealed that this domain, and by extension the CTD heptads and their modifications, is functionally neither absolutely required to maintain pausing in the absence of CDK9 activity nor essential for the release of Pol II into productive elongation.

Original language	English
Pages (from-to)	5489-5498
Number of pages	10
Journal	Journal of Molecular Biology
Volume	432
Issue number	19
Early online date	21 Jul 2020
DOIs	https://doi.org/10.1016/j.jmb.2020.07.010
Publication status	Published - 4 Sept 2020

Funding

We thank Sohail Malik, Evelina Tutucci and Keiichi Ito for their critical reading of the manuscript. This work was supported by NIH grant CA202245 to R.G.R. A.G. was supported by a Swiss National Science Foundation Early Mobility Fellowship (P2GEP3_151952) and by a Human Frontier Science Program Long-Term Fellowship (LT001083/2014). A.G. designed and performed experiments, analyzed and interpreted data and wrote the manuscript. R.G.R supervised the project and wrote the manuscript. The authors declare no competing financial interests.

Funders	Funder number
National Institutes of Health
Human Frontier Science Program	LT001083/2014
National Cancer Institute	R01CA202245
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung	151952, P2GEP3_151952

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title = "The CTD Is Not Essential for the Post-Initiation Control of RNA Polymerase II Activity",

abstract = "Interest in the C-terminal domain (CTD) of the RPB1 subunit of the RNA polymerase II (Pol II) has been revived in recent years, owing to its numerous posttranslational modifications and its “phase-separation” properties. A large number of studies have shown that the status of CTD modifications is associated with the activity of Pol II during the transcription cycle. However, because this domain is essential in living cells, the functional requirement of the full CTD for the control of Pol II activity at endogenous mammalian genes has never been addressed directly in living cells. Using an inducible Pol II-degradation system that we previously established, we investigated here the roles of the CTD in the post-initiation control of Pol II. The selective ablation of the RPB1 CTD, post-initiation, at promoter-proximal pause-sites revealed that this domain, and by extension the CTD heptads and their modifications, is functionally neither absolutely required to maintain pausing in the absence of CDK9 activity nor essential for the release of Pol II into productive elongation.",

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N2 - Interest in the C-terminal domain (CTD) of the RPB1 subunit of the RNA polymerase II (Pol II) has been revived in recent years, owing to its numerous posttranslational modifications and its “phase-separation” properties. A large number of studies have shown that the status of CTD modifications is associated with the activity of Pol II during the transcription cycle. However, because this domain is essential in living cells, the functional requirement of the full CTD for the control of Pol II activity at endogenous mammalian genes has never been addressed directly in living cells. Using an inducible Pol II-degradation system that we previously established, we investigated here the roles of the CTD in the post-initiation control of Pol II. The selective ablation of the RPB1 CTD, post-initiation, at promoter-proximal pause-sites revealed that this domain, and by extension the CTD heptads and their modifications, is functionally neither absolutely required to maintain pausing in the absence of CDK9 activity nor essential for the release of Pol II into productive elongation.

AB - Interest in the C-terminal domain (CTD) of the RPB1 subunit of the RNA polymerase II (Pol II) has been revived in recent years, owing to its numerous posttranslational modifications and its “phase-separation” properties. A large number of studies have shown that the status of CTD modifications is associated with the activity of Pol II during the transcription cycle. However, because this domain is essential in living cells, the functional requirement of the full CTD for the control of Pol II activity at endogenous mammalian genes has never been addressed directly in living cells. Using an inducible Pol II-degradation system that we previously established, we investigated here the roles of the CTD in the post-initiation control of Pol II. The selective ablation of the RPB1 CTD, post-initiation, at promoter-proximal pause-sites revealed that this domain, and by extension the CTD heptads and their modifications, is functionally neither absolutely required to maintain pausing in the absence of CDK9 activity nor essential for the release of Pol II into productive elongation.

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The CTD Is Not Essential for the Post-Initiation Control of RNA Polymerase II Activity

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