Cooperative interaction of transcription termination factors with the RNA polymerase II C-terminal domain

Nat Struct Mol Biol. 2010 Oct;17(10):1195-201. doi: 10.1038/nsmb.1893. Epub 2010 Sep 5.


Phosphorylation of the C-terminal domain (CTD) of RNA polymerase II controls the co-transcriptional assembly of RNA processing and transcription factors. Recruitment relies on conserved CTD-interacting domains (CIDs) that recognize different CTD phosphoisoforms during the transcription cycle, but the molecular basis for their specificity remains unclear. We show that the CIDs of two transcription termination factors, Rtt103 and Pcf11, achieve high affinity and specificity both by specifically recognizing the phosphorylated CTD and by cooperatively binding to neighboring CTD repeats. Single-residue mutations at the protein-protein interface abolish cooperativity and affect recruitment at the 3' end processing site in vivo. We suggest that this cooperativity provides a signal-response mechanism to ensure that its action is confined only to proper polyadenylation sites where Ser2 phosphorylation density is highest.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Conserved Sequence
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Phosphorylation
  • Phosphoserine / chemistry
  • Point Mutation
  • Protein Conformation
  • Protein Interaction Mapping
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • RNA Polymerase II / chemistry
  • RNA Polymerase II / metabolism*
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Serine-Arginine Splicing Factors
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism*
  • Transcription, Genetic
  • mRNA Cleavage and Polyadenylation Factors / chemistry
  • mRNA Cleavage and Polyadenylation Factors / metabolism*


  • NRD1 protein, S cerevisiae
  • Nuclear Proteins
  • PCF11 protein, S cerevisiae
  • Peptide Fragments
  • RNA-Binding Proteins
  • Rtt103 protein, S cerevisiae
  • SCAF8 protein, human
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • mRNA Cleavage and Polyadenylation Factors
  • Serine-Arginine Splicing Factors
  • Phosphoserine
  • RNA Polymerase II