INTS10-INTS13-INTS14 form a functional module of Integrator that binds nucleic acids and the cleavage module

Nat Commun. 2020 Jul 9;11(1):3422. doi: 10.1038/s41467-020-17232-2.


The Integrator complex processes 3'-ends of spliceosomal small nuclear RNAs (snRNAs). Furthermore, it regulates transcription of protein coding genes by terminating transcription after unstable pausing. The molecular basis for Integrator's functions remains obscure. Here, we show that INTS10, Asunder/INTS13 and INTS14 form a separable, functional Integrator module. The structure of INTS13-INTS14 reveals a strongly entwined complex with a unique chain interlink. Unexpected structural homology to the Ku70-Ku80 DNA repair complex suggests nucleic acid affinity. Indeed, the module displays affinity for DNA and RNA but prefers RNA hairpins. While the module plays an accessory role in snRNA maturation, it has a stronger influence on transcription termination after pausing. Asunder/INTS13 directly binds Integrator's cleavage module via a conserved C-terminal motif that is involved in snRNA processing and required for spermatogenesis. Collectively, our data establish INTS10-INTS13-INTS14 as a nucleic acid-binding module and suggest that it brings cleavage module and target transcripts into proximity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / metabolism*
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Ku Autoantigen / chemistry
  • Mutation / genetics
  • Nucleic Acid Conformation
  • Nucleic Acids / metabolism*
  • Protein Binding
  • Protein Domains
  • Protein Multimerization
  • RNA / chemistry
  • RNA / metabolism
  • RNA Processing, Post-Transcriptional
  • Structural Homology, Protein


  • Carrier Proteins
  • Cell Cycle Proteins
  • INTS10 protein, human
  • INTS13 protein, human
  • INTS14 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Nucleic Acids
  • RNA
  • Ku Autoantigen