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. 1. Introduction 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. The vast majority of RNA production in growing cells is carried out by RNA polymerase I (Pol I), which transcribes the precursor of large rRNA, and by RNA polymerase III (Pol III), which transcribes 5S rRNA, tRNA, and some noncoding RNAs. Observation of cryofixed cryosubstituted other sections analyzed by electron microscopy reveals that exponentially growing budding yeast cells contain up to 104 ribosomes per μm3 [1], which represents up to 10% of the cytoplasmic volume [2] (Figure 1(a)). Figure 1: Budding yeast cells and ribosome production. (a) Morphology of Saccharomyces cerevisiae cells after cryofixation and freeze substitution. Ribosomes are individually localized in the cytoplasm (see individual ribosomes detected in the zoomed region). In the nucleus, the nucleolus (No) is detected as a large electron-dense region compared with low electron density of the nucleoplasm (Np). (b) Morphology of the nucleolus. The nucleus appears outlined by a double envelope with pores, and the nucleolus is in close contact with the nuclear envelope. In the nucleolus, a dense fibrillar network is visible throughout the nucleolar volume. Granular components are dispersed throughout the rest of the nucleolus. (c) Visualization of active genes in rDNA. Using a mutant strain with a reduced number of rDNA copies (strain NOY1071; 25 rDNA copies), Miller spreading of total nucleolar DNA allowed single-gene analysis of rRNA genes. (d)
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