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

Mol Cell. 2020 Jul 16;79(2):207-220.e8. doi: 10.1016/j.molcel.2020.05.030. Epub 2020 Jun 15.

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.

Keywords: CTD length; RNA Pol II; phase separation; transcription scaling; transcriptional bursting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Catalytic Domain*
  • Models, Genetic
  • RNA Polymerase II / chemistry
  • RNA Polymerase II / metabolism*
  • RNA-Seq
  • Saccharomycetales / enzymology*
  • Saccharomycetales / genetics*
  • Structure-Activity Relationship
  • Transcription, Genetic*
  • Transcriptome

Substances

  • RNA Polymerase II