Regulation of RNA Polymerase I Transcription in Development, 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 (1), p.51-73
Main Authors: Sharifi, Samim, Bierhoff, Holger
Format: Article
Language:English
Subjects:
Aging
Aging - genetics
Aging - metabolism
Animals
Biosynthesis
Cell Differentiation - genetics
Cell Differentiation - physiology
Cell growth
Chromatin
Chromatin - genetics
Chromatin - metabolism
DNA, Ribosomal - genetics
DNA, Ribosomal - metabolism
DNA-directed RNA polymerase
Epigenesis, Genetic
Epigenetics
Eukaryotes
Gene expression
Gene regulation
Genes
Humans
Models, Biological
Multigene Family
Neoplasms - genetics
Neoplasms - metabolism
Nucleoli
Pluripotent Stem Cells - cytology
Pluripotent Stem Cells - metabolism
Ribonucleic acid
Ribosomes - genetics
Ribosomes - metabolism
RNA
RNA polymerase
RNA Polymerase I - genetics
RNA Polymerase I - metabolism
RNA, Ribosomal - genetics
RNA, Ribosomal - metabolism
rRNA
Signal Transduction
Transcription
Transcription factors
Transcription, Genetic
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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