RNA Pol II Length and Disorder Enable Cooperative Scaling of Transcriptional Bursting
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.
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.Attached Files
Submitted - 825299.full.pdf
Supplemental Material - 1-s2.0-S1097276520303506-mmc1.pdf
Supplemental Material - 1-s2.0-S1097276520303506-mmc2.csv
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Additional details
- Eprint ID
- 99592
- Resolver ID
- CaltechAUTHORS:20191031-131636300
- Howard Hughes Medical Institute (HHMI)
- Gordon Ross Medical Foundation
- Donna and Benjamin M. Rosen Bioengineering Center
- Caltech Beckman Institute
- Millard and Muriel Jacobs Genetics and Genomics Laboratory
- Created
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2019-10-31Created from EPrint's datestamp field
- Updated
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2023-06-01Created from EPrint's last_modified field
- Caltech groups
- Millard and Muriel Jacobs Genetics and Genomics Laboratory, Rosen Bioengineering Center, Division of Biology and Biological Engineering