Regulation of ribosomal RNA gene copy number, transcription and nucleolus organization in eukaryotes

One of the first biological machineries to be created seems to have been the ribosome. Since then, organisms have dedicated great efforts to optimize this apparatus. The ribosomal RNA (rRNA) contained within ribosomes is crucial for protein synthesis and maintenance of cellular function in all known organisms. In eukaryotic cells, rRNA is produced from ribosomal DNA clusters of tandem rRNA genes, whose organization in the nucleolus, maintenance and transcription are strictly regulated to satisfy the substantial demand for rRNA required for ribosome biogenesis. Recent studies have elucidated mechanisms underlying the integrity of ribosomal DNA and regulation of its transcription, including epigenetic mechanisms and a unique recombination and copy-number control system to stably maintain high rRNA gene copy number. In this Review, we disucss how the crucial maintenance of rRNA gene copy number through control of gene amplification and of rRNA production by RNA polymerase I are orchestrated. We also discuss how liquid-liquid phase separation controls the architecture and function of the nucleolus and the relationship between rRNA production, cell senescence and disease. Ribosome biogenesis, including ribosomal RNA (rRNA) production, occurs in the nucleolus. Recent studies have revealed how the integrity and copy number of rRNA genes is maintained through a unique recombination system, how rRNA transcription is regulated and how phase separation orchestrates nucleolus function.

Automated summary

Ribosome, one of the earliest biological machineries, is crucial for protein synthesis and cellular function. Recent studies have revealed the mechanisms of maintaining the integrity and copy number of ribosomal DNA, the regulation of ribosomal RNA transcription, as well as the role of liquid-liquid phase separation in nucleolus function. The relationship between ribosomal RNA production, cell senescence, and disease is also discussed.