Structural basis of Integrator-mediated transcription regulation

Science. 2021 Nov 12;374(6569):883-887. doi: 10.1126/science.abk0154. Epub 2021 Nov 11.


Integrator and protein phosphatase 2A (PP2A) form a complex that dephosphorylates paused RNA polymerase II (Pol II), cleaves the nascent RNA, and terminates transcription. We report the structure of the pretermination complex containing the human Integrator-PP2A complex bound to paused Pol II. Integrator binds Pol II and the pausing factors DSIF and NELF to exclude binding of the elongation factors SPT6 and PAF1 complex. Integrator also binds the C-terminal domain of Pol II and positions PP2A to counteract Pol II phosphorylation and elongation. The Integrator endonuclease docks to the RNA exit site and opens to cleave nascent RNA about 20 nucleotides from the Pol II active site. Integrator does not bind the DNA clamps formed by Pol II and DSIF, enabling release of DNA and transcription termination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cryoelectron Microscopy
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism
  • Endoribonucleases / chemistry
  • Endoribonucleases / metabolism
  • Gene Expression Regulation*
  • Humans
  • Models, Molecular
  • Multiprotein Complexes / chemistry*
  • Multiprotein Complexes / metabolism
  • Protein Binding
  • Protein Conformation
  • Protein Domains
  • Protein Phosphatase 2 / chemistry*
  • Protein Phosphatase 2 / metabolism
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • RNA / metabolism
  • RNA Polymerase II / chemistry*
  • RNA Polymerase II / metabolism
  • Transcription, Genetic*


  • DNA-Binding Proteins
  • Multiprotein Complexes
  • Protein Subunits
  • RNA
  • RNA Polymerase II
  • Endoribonucleases
  • INTS11 protein, human
  • Protein Phosphatase 2