Fig. 1
From: Ribosomal proteins and human diseases: molecular mechanisms and targeted therapy
A schematic representation of ribosome biogenesis in mammalian cells. a Ribosome biogenesis is a tightly coordinated process involving all three RNA polymerases (Pol I, Pol II, and Pol III). RNA Pol I transcribes the ribosomal RNA (rRNA) genes (rDNA) to produce the 47S precursor rRNA (47S pre-rRNA) transcript in the nucleolus. Pol I transcription initiation involves binding of the upstream binding factor (UBF) to the core promoter region (core) and upstream control element (UCE) of the rDNA promoters and facilitating the recruitment and binding of the selectivity factor 1 (SL-1) complex. SL-1 is composed of the TATA-box-binding protein (TBP) and five Pol I-specific TATA-box-associated factors (TAFs). This complex in turn recruits the Pol I-specific initiation factor RRN3, which associates with DNA topoisomerase IIα (TOPIIα) and Pol I to complete assembly of a transcriptionally-competent Pol I complex. Following transcription, the 47S pre-rRNA is subsequently cleaved and processed into the mature 18S, 5.8S, and 28S rRNA species. These molecules are then assembled along with ribosomal proteins and the 5S rRNA produced by Pol II and III, respectively, to form the major catalytic and architectural components of the small (40S) and the large (60S) ribosomal subunits. Once assembled, ribosomal complexes are exported from the nucleolus to the cytoplasm, where they form the mature (80S) ribosome required to initiate mRNA translation and thus protein synthesis. b A diverse range of anticancer drugs target ribosome biogenesis by inhibiting Pol I transcription and/or pre-rRNA processing
