Quintero-Cadena, Porfirio and Lenstra, Tineke L. and Sternberg, Paul W. (2020) RNA Pol II Length and Disorder Enable Cooperative Scaling of Transcriptional Bursting. Molecular Cell, 79 (2). pp. 207-220. ISSN 1097-2765. https://resolver.caltech.edu/CaltechAUTHORS:20191031-131636300
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Abstract
RNA polymerase II (RNA Pol II) contains a disordered C-terminal domain (CTD) whose length enigmatically correlates with genome size. The CTD is crucial to eukaryotic transcription, yet the functional and evolutionary relevance of this variation remains unclear. Here, we investigate how CTD length and disorder influence transcription. We find that length modulates the size and frequency of transcriptional bursting. Disorder is highly conserved and facilitates CTD-CTD interactions, an ability we show is separable from protein sequence and necessary for efficient transcription. We build a data-driven quantitative model, simulations of which recapitulate experiments and support that CTD length promotes initial polymerase recruitment to the promoter and slows down its release from it and that CTD-CTD interactions enable recruitment of multiple polymerases. Our results reveal how these parameters provide access to a range of transcriptional activity, offering a new perspective for the mechanistic significance of CTD length and disorder in transcription across eukaryotes.
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Additional Information: | © 2020 Elsevier Inc. Received 30 October 2019, Revised 9 April 2020, Accepted 19 May 2020, Available online 15 June 2020. We thank Mitchell Guttman, Matt Thomson, and members of the Sternberg laboratory for helpful discussions; Heun J. Lee, Andres Collazo, and Giada Spigolon for imaging assistance; Igor Antoshechkin and Vijaya Kumar for RNA-seq experiments; and Steven Mcknight and Masato Kato for reagents. This work was supported by the Howard Hughes Medical Institute, with which P.W.S. was an investigator; the Gordon Ross Medical Foundation and Benjamin M. Rosen graduate fellowships; the Biological Imaging Center at the Caltech Beckman Institute; and the Millard and Muriel Jacobs Genetics and Genomics Laboratory. Author Contributions: Conceptualization, P.Q.-C. and P.W.S.; Methodology, P.Q.-C., P.W.S., and T.L.L.; Software, P.Q.-C.; Formal Analysis, P.Q.-C. and T.L.L.; Investigation, P.Q.-C.; Data Curation, P.Q.-C.; Writing – Original Draft, P.Q.-C. and P.W.S.; Writing – Review & Editing, P.Q.-C., P.W.S., and T.L.L.; Visualization, P.Q.-C.; Supervision, P.W.S.; Funding Acquisition, P.W.S. The authors declare no competing interests. | ||||||||||||
Group: | Millard and Muriel Jacobs Genetics and Genomics Laboratory, Rosen Bioengineering Center | ||||||||||||
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Subject Keywords: | transcriptional bursting; RNA Pol II; CTD length; phase separation; transcription scaling | ||||||||||||
Issue or Number: | 2 | ||||||||||||
Record Number: | CaltechAUTHORS:20191031-131636300 | ||||||||||||
Persistent URL: | https://resolver.caltech.edu/CaltechAUTHORS:20191031-131636300 | ||||||||||||
Official Citation: | Porfirio Quintero-Cadena, Tineke L. Lentra, Paul W. Sternberg, RNA Pol II Length and Disorder Enable Cooperative Scaling of Transcriptional Bursting, Molecular Cell, Volume 79, Issue 2, 2020, Pages 207-220.e8, ISSN 1097-2765, https://doi.org/10.1016/j.molcel.2020.05.030. (http://www.sciencedirect.com/science/article/pii/S1097276520303506) | ||||||||||||
Usage Policy: | No commercial reproduction, distribution, display or performance rights in this work are provided. | ||||||||||||
ID Code: | 99592 | ||||||||||||
Collection: | CaltechAUTHORS | ||||||||||||
Deposited By: | Tony Diaz | ||||||||||||
Deposited On: | 31 Oct 2019 20:36 | ||||||||||||
Last Modified: | 17 Jul 2020 22:08 |
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