Age-dependent ribosomal DNA variations in mice

Eriko Watada, Sihan Li, Yutaro Hori, Katsunori Fujiki, Katsuhiko Shirahige, Toshifumi Inada, Takehiko Kobayashi

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


The rRNA gene, which consists of tandem repetitive arrays (ribosomal DNA [rDNA] repeat), is one of the most unstable regions in the genome. The rDNA repeat in the budding yeast Saccharomyces cerevisiae is known to become unstable as the cell ages. However, it is unclear how the rDNA repeat changes in aging mammalian cells. Using quantitative single-cell analyses, we identified age-dependent alterations in rDNA copy number and levels of methylation in mice. The degree of methylation and copy number of rDNA from bone marrow cells of 2-year-old mice were increased by comparison to levels in 4-week-old mice in two mouse strains, BALB/cA and C57BL/6. Moreover, the level of pre-rRNA transcripts was reduced in older BALB/cA mice. We also identified many sequence variations in the rDNA. Among them, three mutations were unique to old mice, and two of them were found in the conserved region in budding yeast. We established yeast strains with the old-mouse-specific mutations and found that they shortened the life span of the cells. Our findings suggest that rDNA is also fragile in mammalian cells and that alterations within this region have a profound effect on cellular function.

Original languageEnglish
Article numbere0036820
JournalMolecular and cellular biology
Issue number22
Publication statusPublished - 2020 Nov


  • DNA methylation
  • Genome instability
  • Mouse
  • Mutation rate
  • Ribosomal RNA gene
  • Senescence
  • Yeast life span
  • rDNA copy number

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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