Regulation of Ribosomal RNA Production by RNA Polymerase I: Does Elongation Come First?

Benjamin Albert,Jorge Perez-Fernandez,Olivier Gadal,Isabelle Léger-Silvestre

doi:10.1155/2012/276948

Abstract

Ribosomal RNA (rRNA) production represents the most active transcription in the cell. Synthesis of the large rRNA precursors (35–47S) can be achieved by up to 150 RNA polymerase I (Pol I) enzymes simultaneously transcribing each rRNA gene. In this paper, we present recent advances made in understanding the regulatory mechanisms that control elongation. Built-in Pol I elongation factors, such as Rpa34/Rpa49 in budding yeast and PAF53/CAST in humans, are instrumental to the extremely high rate of rRNA production per gene. rRNA elongation mechanisms are intrinsically linked to chromatin structure and to the higher-order organization of the rRNA genes (rDNA). Factors such as Hmo1 in yeast and UBF1 in humans are key players in rDNA chromatin structure in vivo. Finally, elongation factors known to regulate messengers RNA production by RNA polymerase II are also involved in rRNA production and work cooperatively with Rpa49 in vivo.

Highlights

IntroductionThree RNA polymerases transcribe the genome. The most importance is placed on RNA polymerase II (Pol II), which is responsible for synthesizing mRNA and a large variety of noncoding RNAs
In cell nuclei, three RNA polymerases transcribe the genome
The most importance is placed on RNA polymerase II (Pol II), which is responsible for synthesizing mRNA and a large variety of noncoding RNAs

Summary

Introduction

Three RNA polymerases transcribe the genome. The most importance is placed on RNA polymerase II (Pol II), which is responsible for synthesizing mRNA and a large variety of noncoding RNAs. UBF1 and Hmo might have a conserved function in stimulating Pol I elongation (Albert et al submitted) Both human and yeast Pol I enzymes are unable to initiate productive RNA synthesis with only promoter-bound factors [29, 30]. In a partially purified in vitro system, this fusion, called CARA, led to a constitutively active Pol I even during stress, showing that Pol I complexed with Rrn is initiation competent even under conditions known to inhibit ribosome production [39]. A nondegradable form of Rrn, missing this PEST motif, attenuated the reduction in initiation competent Pol I-Rrn3p complexes observed upon nutrient depletion Such a mutation should mimic the CARA mutant phenotype. A subunit of the Rrn core factor binds RPG promoters, suggesting a coupling between rRNA production and RPG transcription [49]. We will extensively describe how the rRNA elongation step might be regulated to integrate all the complex processes necessary to achieve this early step of ribosome assembly

Early Ribosome Assembly Occurs during rDNA Transcription

Epigenetic Regulation and Chromatin Status of rDNA

Regulator of Pol I Elongation

Findings

Concluding Remarks