Expression of RNA polymerase I catalytic core is influenced by RPA12.

Abstract

RNA Polymerase I (Pol I) has recently been recognized as a cancer therapeutic target. The activity of this enzyme is essential for ribosome biogenesis and is universally activated in cancers. The enzymatic activity of this multi-subunit complex resides in its catalytic core composed of RPA194, RPA135, and RPA12, a subunit with functions in RNA cleavage, transcription initiation and elongation. Here we explore whether RPA12 influences the regulation of RPA194 in human cancer cells. We use a specific small-molecule Pol I inhibitor BMH-21 that inhibits transcription initiation, elongation and ultimately activates the degradation of Pol I catalytic subunit RPA194. We show that silencing RPA12 causes alterations in the expression and localization of Pol I subunits RPA194 and RPA135. Furthermore, we find that despite these alterations not only does the Pol I core complex between RPA194 and RPA135 remain intact upon RPA12 knockdown, but the transcription of Pol I and its engagement with chromatin remain unaffected. The BMH-21-mediated degradation of RPA194 was independent of RPA12 suggesting that RPA12 affects the basal expression, but not the drug-inducible turnover of RPA194. These studies add to knowledge defining regulatory factors for the expression of this Pol I catalytic subunit.

• Authors: Brittany L Ford, Ting Wei, Hester Liu, Catherine E Scull, Saman M Najmi, Stephanie Pitts, Wenjun Fan, David A Schneider, Marikki Laiho
• Journal: PloS one (PLoS One) Vol. 18 Issue 5 Pg. e0285660 ( 2023) ISSN: 1932-6203 [Electronic] United States
• PMID: 37167337 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright: © 2023 Ford et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Chemical References

• Chromatin
• RNA Polymerase I
• RNA Polymerase II

Topics

• Humans
• Catalytic Domain
• Chromatin
• RNA Polymerase I (genetics, metabolism)
• RNA Polymerase II (metabolism)
• Transcription, Genetic
• Neoplasms (genetics, metabolism)