2023/11/27 by Chaïma Azouzi, Katrin Schwank, Sophie Queillé +9 · 1 voice
Biochemistry, Genetics and Molecular Biology · #RNA Research and Splicing #RNA and protein synthesis mechanisms #RNA modifications and cancer
paper · pdf · doi:10.1101/2023.11.27.568781
openalex publication_date 2023/11/27 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
ABSTRACT The RNA polymerase I (Pol I) enzyme that synthesizes large rRNA precursors, exhibits high rate of pauses during elongation, indicative of a discontinuous process. We show here that Premature Termination of Transcription (PTT) by Pol I is a critical regulatory step limiting rRNA production in vivo . The Pol I mutant, SuperPol (RPA135-F301S), produces 1.5-fold more rRNA than the wild type (WT). Combined CRAC and rRNA analysis link increased rRNA production in SuperPol to reduced PTT, resulting in shifting polymerase distribution toward the 3’ end of rDNA genes. In vitro , SuperPol shows reduced nascent transcript cleavage, associated with more efficient transcript elongation after pauses, to the detriment of transcriptional fidelity. Notably, SuperPol is resistant to BMH-21, a drug impairing Pol I elongation and inducing proteasome-mediated degradation of Pol I subunits. Compared to WT, SuperPol maintains subunit stability and sustains high transcription levels upon BMH-21 treatment. These comparative results show that PTT is alleviated in SuperPol while it is stimulated by BMH-21 in WT Pol I.