Ribosomal RNA synthesis machinery

The ribosomal RNA (rRNA) synthesis machinery is a complex assembly of proteins, primarily centered around RNA Polymerase I (Pol I), responsible for the transcription of ribosomal DNA (rDNA) into precursor rRNA (45S pre-rRNA). This process is the rate-limiting step in ribosome biogenesis and is essential for maintaining the protein synthesis capacity required for cell growth and division (Bywater et al., 2013). In many cancers, the rRNA synthesis machinery is hyperactivated to support the rapid proliferation of malignant cells, making it an attractive therapeutic target. Drugs targeting this machinery, such as CX-5461 (Pidnarulex) and BMH-21, work by selectively inhibiting Pol I transcription, which triggers nucleolar stress and subsequent cell cycle arrest or apoptosis (Drygin et al., 2011; Peltonen et al., 2014). This approach is particularly effective in tumors with high biosynthetic demands or those sensitive to the activation of the p53 pathway. Clinical development of these inhibitors focuses on both hematologic malignancies and solid tumors, though challenges include managing systemic toxicities related to the inhibition of a fundamental cellular process. Additionally, the machinery's role in ribosomopathies like Diamond-Blackfan anemia suggests potential for broader therapeutic applications beyond oncology (Peltonen et al., 2014).

Other names

RNA polymerase I transcription machineryrDNA transcription complexPol I machineryRibosome biogenesis machinery

Inhibition of RNA polymerase I (Pol I) mediated transcription of ribosomal DNA (rDNA) into precursor ribosomal RNA (45S pre-rRNA), leading to nucleolar stress and activation of p53-dependent or independent apoptosis (Drygin et al., 2011; Peltonen et al., 2014).