Regulation of RNA Polymerase I TranscriptioninDevelopment, Disease, and Aging

Ribosome biogenesis is a complex and highly energy-demanding process that requires the concerted action of all three nuclear RNA polymerases (Pol I-III) in eukaryotes. The three largest ribosomal RNAs (rRNAs) originate from a precursor transcript (pre-rRNA) that is encoded by multicopy genes located...

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Bibliographic Details
Published in:Annual review of biochemistry 2018-06, Vol.87, p.51-73
Main Authors: Sharifi, Samim, Bierhoff, Holger
Format: Article
Language:English
Subjects:
aging
cell proliferation
epigenetic regulation
Pol I transcription machinery
ribosome biogenesis
rRNA synthesis
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Summary:Ribosome biogenesis is a complex and highly energy-demanding process that requires the concerted action of all three nuclear RNA polymerases (Pol I-III) in eukaryotes. The three largest ribosomal RNAs (rRNAs) originate from a precursor transcript (pre-rRNA) that is encoded by multicopy genes located in the nucleolus. Transcription of these rRNA genes (rDNA) by Pol I is the key regulation step in ribosome production and is tightly controlled by an intricate network of signaling pathways and epigenetic mechanisms. In this article, we give an overview of the composition of the basal Pol I machinery and rDNA chromatin. We discuss rRNA gene regulation in response to environmental signals and developmental cues and focus on perturbations occurring in diseases linked to either excessive or limited rRNA levels. Finally, we discuss the emerging view that rDNA integrity and activity may be involved in the aging process.
ISSN:0066-4154
1545-4509
DOI:10.1146/annurev-biochem-062917-012612