Nucleolar Pol II Interactome Reveals TBPL1, PAF1, and Pol I at Intergenic RDNA Drive RRNA Biogenesis

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Nov 6

PMID 39505901

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

RNA polymerase II-mediated rDNA transcription mediates rDNA copy number expansion in Drosophila.

Watase G, Yamashita Y PLoS Genet. 2024; 20(5):e1011136.

PMID: 38758955 PMC: 11139327. DOI: 10.1371/journal.pgen.1011136.

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