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RNA Pol II Length and Disorder Enable Cooperative Scaling of Transcriptional Bursting

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.molcel.2020.05.030DOIArticle
https://doi.org/10.1101/825299DOIDiscussion Paper
https://github.com/WormLabCaltechRelated ItemData/Code
ORCID:
AuthorORCID
Quintero-Cadena, Porfirio0000-0003-0067-5844
Lenstra, Tineke L.0000-0002-4440-9962
Sternberg, Paul W.0000-0002-7699-0173
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
Funders:
Funding AgencyGrant Number
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Gordon Ross Medical FoundationUNSPECIFIED
Donna and Benjamin M. Rosen Bioengineering CenterUNSPECIFIED
Caltech Beckman InstituteUNSPECIFIED
Millard and Muriel Jacobs Genetics and Genomics LaboratoryUNSPECIFIED
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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