- RNA polymerase I (Pol I) is a specialized enzyme responsible for the transcription of ribosomal RNA (rRNA) genes, specifically the large precursor rRNA transcript in eukaryotic cells.
- This enzyme is a key player in ribosome biogenesis, as it synthesizes the 47S pre-rRNA in mammals (or 35S in yeast), which is subsequently processed into the mature 18S, 5.8S, and 28S rRNAs.
- These rRNAs are integral components of ribosomes, making Pol I activity essential for cellular protein synthesis and overall cell growth.
- Pol I is a multi-subunit complex composed of 14 subunits in humans, many of which are homologous to those found in the other eukaryotic RNA polymerases (Pol II and Pol III), but with certain subunits unique to Pol I that facilitate its specialized function.
- Unlike RNA polymerase II, which transcribes a wide variety of genes including mRNAs, Pol I is dedicated almost exclusively to a single type of gene—the rDNA—organized into tandemly repeated clusters within nucleolar organizer regions (NORs) on specific chromosomes. These regions serve as the foundation for nucleolar formation and function.
- Transcription by RNA polymerase I is tightly regulated and highly efficient. It begins with the assembly of the pre-initiation complex at the rDNA promoter, a process that requires several transcription factors, including upstream binding factor (UBF) and selectivity factor 1 (SL1). UBF binds to the rDNA promoter and induces a DNA conformation favorable for transcription, while SL1 stabilizes the binding of Pol I to the promoter and ensures proper initiation. Once transcription begins, Pol I rapidly synthesizes the long pre-rRNA transcript, which contains the sequences for the 18S, 5.8S, and 28S rRNAs, interspersed with non-coding spacers.
- Pol I activity is tightly linked to cellular growth and proliferation. Because ribosome production is energy-intensive and critical for protein synthesis, cells adjust Pol I transcriptional activity in response to nutrient availability, growth signals, and stress. In rapidly dividing cells, such as cancer cells, Pol I is often upregulated to meet increased demands for protein synthesis. Conversely, during stress conditions or nutrient deprivation, Pol I activity is downregulated to conserve resources.
