A ubiquitous disordered protein interaction module orchestrates transcription elongation

Science. 2021 Nov 26;374(6571):1113-1121. doi: 10.1126/science.abe2913. Epub 2021 Nov 25.


During eukaryotic transcription elongation, RNA polymerase II (RNAP2) is regulated by a chorus of factors. Here, we identified a common binary interaction module consisting of TFIIS N-terminal domains (TNDs) and natively unstructured TND-interacting motifs (TIMs). This module was conserved among the elongation machinery and linked complexes including transcription factor TFIIS, Mediator, super elongation complex, elongin, IWS1, SPT6, PP1-PNUTS phosphatase, H3K36me3 readers, and other factors. Using nuclear magnetic resonance, live-cell microscopy, and mass spectrometry, we revealed the structural basis for these interactions and found that TND-TIM sequences were necessary and sufficient to induce strong and specific colocalization in the crowded nuclear environment. Disruption of a single TIM in IWS1 induced robust changes in gene expression and RNAP2 elongation dynamics, which underscores the functional importance of TND-TIM surfaces for transcription elongation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / metabolism
  • Cell Line, Tumor
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism
  • Gene Expression
  • Humans
  • Intrinsically Disordered Proteins / chemistry*
  • Intrinsically Disordered Proteins / metabolism
  • Models, Molecular
  • Mutation
  • Protein Binding
  • Protein Domains
  • Protein Interaction Domains and Motifs / genetics
  • Protein Interaction Maps
  • RNA Polymerase II / chemistry
  • RNA Polymerase II / metabolism*
  • RNA-Binding Proteins / chemistry*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Transcription Elongation, Genetic*
  • Transcription Factors / chemistry*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptional Elongation Factors / chemistry*
  • Transcriptional Elongation Factors / metabolism


  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • Intrinsically Disordered Proteins
  • Iws1 protein, human
  • PPP1R10 protein, human
  • PSIP1 protein, human
  • RNA-Binding Proteins
  • Transcription Factors
  • Transcriptional Elongation Factors
  • transcription factor S-II
  • RNA Polymerase II