RNA polymerase I transcription complex (Pol I transcription complex)

The RNA polymerase I (Pol I) transcription complex is a specialized multi-subunit assembly located within the nucleolus that is responsible for transcribing ribosomal DNA (rDNA) into the 45S precursor ribosomal RNA (rRNA). This process is the rate-limiting step in ribosome biogenesis, which is essential for protein synthesis and cellular growth (Ruggero & Pandolfi, 2003). The complex is recruited to the GC-rich promoter regions of rDNA by key transcription factors, including the Upstream Binding Factor (UBF) and Selectivity Factor 1 (SL1) (Drygin et al., 2011). In many cancers, Pol I transcription is significantly upregulated to meet the high metabolic demands of rapidly proliferating cells, making it a distinct therapeutic vulnerability (Bywater et al., 2012). Drugs targeting this complex, such as CX-5461, often exploit the high GC content of rDNA by stabilizing G-quadruplex structures, thereby blocking Pol I progression and triggering a nucleolar stress response (Xu et al., 2017). This disruption leads to the activation of p53-dependent and independent apoptotic pathways, providing a selective mechanism to eliminate cancer cells while potentially sparing normal cells with lower ribosome synthesis requirements (Peltonen et al., 2014; Quin et al., 2014).

Other names

GC-rich ribosomal DNA transcription complexrDNA transcription machineryRNA polymerase I pre-initiation complexNucleolar transcription complex

Inhibition of RNA polymerase I-mediated transcription of ribosomal DNA, often through stabilization of G-quadruplexes in GC-rich rDNA sequences or direct disruption of the Pol I complex assembly and elongation.