Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published July 16, 2020 | Supplemental Material + Submitted
Journal Article Open

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


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


Files (22.6 MB)
Name Size Download all
14.2 MB Preview Download
8.5 MB Preview Download
2.2 kB Preview Download

Additional details

August 22, 2023
December 22, 2023