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

Author

Listed:
  • Kevin Sabath

    (ETH Zurich)

  • Melanie L. Stäubli

    (ETH Zurich)

  • Sabrina Marti

    (ETH Zurich)

  • Alexander Leitner

    (ETH Zurich)

  • Murielle Moes

    (ETH Zurich)

  • Stefanie Jonas

    (ETH Zurich)

Abstract

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.

Suggested Citation

  • Kevin Sabath & Melanie L. Stäubli & Sabrina Marti & Alexander Leitner & Murielle Moes & Stefanie Jonas, 2020. "INTS10–INTS13–INTS14 form a functional module of Integrator that binds nucleic acids and the cleavage module," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17232-2
    DOI: 10.1038/s41467-020-17232-2
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    Cited by:

    1. Min-Han Lin & Madeline K. Jensen & Nathan D. Elrod & Kai-Lieh Huang & Kevin A. Welle & Eric J. Wagner & Liang Tong, 2022. "Inositol hexakisphosphate is required for Integrator function," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    2. Xiao Chen & Yinglu Li & Fang Zhu & Xinjing Xu & Brian Estrella & Manuel A. Pazos & John T. McGuire & Dimitris Karagiannis & Varun Sahu & Mustafo Mustafokulov & Claudio Scuoppo & Francisco J. Sánchez-R, 2023. "Context-defined cancer co-dependency mapping identifies a functional interplay between PRC2 and MLL-MEN1 complex in lymphoma," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. Kenneth Bødkter Schou & Samuel Mandacaru & Muhammad Tahir & Nikola Tom & Ann-Sofie Nilsson & Jens S. Andersen & Matteo Tiberti & Elena Papaleo & Jiri Bartek, 2024. "Exploring the structural landscape of DNA maintenance proteins," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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