Expression of RNA polymerase I catalytic core is influenced by RPA12

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.

 

Comments: 

The information you provided describes a study exploring the role of RPA12 in the regulation of RNA Polymerase I (Pol I) in human cancer cells. Pol I is an enzyme responsible for ribosome biogenesis, and its activity is often increased in cancer cells. The catalytic core of Pol I is composed of three subunits: RPA194, RPA135, and RPA12. In this study, the researchers investigated how RPA12 influences the regulation of RPA194 in cancer cells and also explored the effects of a specific small-molecule Pol I inhibitor called BMH-21.

The researchers found that silencing RPA12 led to changes in the expression and localization of RPA194 and RPA135, the other subunits of the Pol I core complex. Despite these alterations, the interaction between RPA194 and RPA135 remained intact, and the transcription of Pol I and its binding to chromatin (the DNA-protein complex) were not affected. This suggests that RPA12 plays a role in the basal expression of RPA194 but does not influence its drug-inducible degradation.

Additionally, the study showed that treatment with the Pol I inhibitor BMH-21 resulted in the degradation of RPA194, independent of RPA12. This indicates that RPA12 does not affect the drug-induced turnover of RPA194 but rather affects its basal expression.

Overall, these findings contribute to our understanding of the regulatory factors involved in the expression of the Pol I catalytic subunit, RPA194, and highlight the potential of targeting Pol I, particularly RPA194, as a therapeutic strategy in cancer treatment.