The RNA polymerase I transcription machinery

Abstract

The rRNAs constitute the catalytic and structural components of the ribosome, the protein synthesis machinery of cells. The level of rRNA synthesis, mediated by Pol I (RNA polymerase I), therefore has a major impact on the life and destiny of a cell. In order to elucidate how cells achieve the stringent control of Pol I transcription, matching the supply of rRNA to demand under different cellular growth conditions, it is essential to understand the components and mechanics of the Pol I transcription machinery. In this review, we discuss: (i) the molecular composition and functions of the Pol I enzyme complex and the two main Pol I transcription factors, SL1 (selectivity factor 1) and UBF (upstream binding factor); (ii) the interplay between these factors during pre-initiation complex formation at the rDNA promoter in mammalian cells; and (iii) the cellular control of the Pol I transcription machinery.

Figure 1. The Pol I transcription cycle

The TBP–TAF complex SL1 interacts stably with the rDNA promoter, near the start site of transcription (black arrow). Dimers of UBF interact dynamically with rDNA promoter elements (grey arrows), such that UBF–rDNA complexes might be relatively short-lived. UBF and SL1 interact co-operatively at the promoter elements, and SL1 reduces the dissociation of UBF from the rDNA, thereby increasing the residence time of UBF at the promoter (1). rDNA promoter topology is altered dramatically by UBF binding. SL1 in the UBF–SL1–rDNA complex recruits the initiation-competent Pol I–hRRN3 complex Pol Iβ through the interactions of TAF_I subunits with hRRN3. This culminates in formation of the complete PIC, poised for initiation of transcription (2). UBF stimulates the promoter escape/clearance of Pol I. In the transition from initiation to elongation, hRRN3 dissociates from Pol I, and the Pol I enzyme is converted into a transcript-elongating enzyme complex, Pol Iε (3). SL1 and UBF remain promoter-bound following promoter clearance by Pol I (4) and, thus, can function as a re-initiation scaffold (5), to allow multiple rounds of transcription from the same rDNA promoter. Pol Iε transcription terminates and rRNA is released at termination sites (black rectangle on rDNA); this process is directed by TTF-I (transcription termination factor-I) and PTRF (polymerase I and transcript release factor). Following termination of transcription, it is possible that the spent Pol I complex is converted back into initiation-competent Pol Iβ and thence recruited to the rDNA promoter by SL1 to initiate a new round of transcription (6).