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Nucleolar Pol II interactome reveals TBPL1, PAF1, and Pol I at intergenic rDNA drive rRNA biogenesis

Author

Listed:
  • Negin Khosraviani

    (University of Toronto)

  • V. Talya Yerlici

    (University of Toronto)

  • Jonathan St-Germain

    (University Health Network
    University of Toronto)

  • Yi Yang Hou

    (University of Toronto)

  • Shi Bo Cao

    (University of Toronto)

  • Carla Ghali

    (University of Toronto)

  • Michael Bokros

    (University of Miami
    University of Miami)

  • Rehna Krishnan

    (University Health Network
    University of Toronto)

  • Razqallah Hakem

    (University Health Network
    University of Toronto)

  • Stephen Lee

    (University of Miami
    University of Miami)

  • Brian Raught

    (University Health Network
    University of Toronto)

  • Karim Mekhail

    (University of Toronto
    University of Toronto
    The Royal Society of Canada)

Abstract

Ribosomal DNA (rDNA) repeats harbor ribosomal RNA (rRNA) genes and intergenic spacers (IGS). RNA polymerase (Pol) I transcribes rRNA genes yielding rRNA components of ribosomes. IGS-associated Pol II prevents Pol I from excessively synthesizing IGS non-coding RNAs (ncRNAs) that can disrupt nucleoli and rRNA production. Here, compartment-enriched proximity-dependent biotin identification (compBioID) revealed the TATA-less-promoter-binding TBPL1 and transcription-regulatory PAF1 with nucleolar Pol II. TBPL1 localizes to TCT motifs, driving Pol II and Pol I and maintaining its baseline ncRNA levels. PAF1 promotes Pol II elongation, preventing unscheduled R-loops that hyper-restrain IGS Pol I-associated ncRNAs. PAF1 or TBPL1 deficiency disrupts nucleolar organization and rRNA biogenesis. In PAF1-deficient cells, repressing unscheduled IGS R-loops rescues nucleolar organization and rRNA production. Depleting IGS Pol I-dependent ncRNAs is sufficient to compromise nucleoli. We present the nucleolar interactome of Pol II and show that its regulation by TBPL1 and PAF1 ensures IGS Pol I ncRNAs maintaining nucleolar structure and function.

Suggested Citation

  • Negin Khosraviani & V. Talya Yerlici & Jonathan St-Germain & Yi Yang Hou & Shi Bo Cao & Carla Ghali & Michael Bokros & Rehna Krishnan & Razqallah Hakem & Stephen Lee & Brian Raught & Karim Mekhail, 2024. "Nucleolar Pol II interactome reveals TBPL1, PAF1, and Pol I at intergenic rDNA drive rRNA biogenesis," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54002-w
    DOI: 10.1038/s41467-024-54002-w
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    References listed on IDEAS

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