Abstract
rDNA loci, composed of hundreds of tandemly duplicated arrays of rRNA genes, are known to be among the most unstable genetic elements due to their repetitive nature. rDNA instability underlies aging (replicative senescence) in yeast cells, however, its contribution to the aging of multicellular organisms is poorly understood. In this study, we investigate the dynamics of rDNA loci during aging in the Drosophila male germline stem cell (GSC) lineage, and show that rDNA copy number decreases during aging. Our study further reveals that this age-dependent decrease in rDNA copy number is heritable from generation to generation, yet GSCs in young animals that inherited reduced rDNA copy number are capable of recovering normal rDNA copy number. Based on these findings, we propose that rDNA loci are dynamic genetic elements, where rDNA copy number changes dynamically yet is maintained through a recovery mechanism in the germline.
Highlights
The ribosomal DNA loci consist of tandem repetitive arrays of the rRNA genes, which code for the mature RNA components of ribosomes, flanked by intergenic spacer sequences (IGS) (Figure 1A). rDNA loci are considered to be one of the most unstable regions of the genome due to their repetitive nature and high transcriptional activity
We investigate the dynamics of the rDNA loci during aging in Drosophila male germline stem cells (GSCs)
We found that the frequency of GSCs with normal nucleolar morphology progressively decreased during aging throughout 40 days of adulthood (Figure 1C), as the GSCs with abnormal nucleolar morphology increased
Summary
The ribosomal DNA (rDNA) loci consist of tandem repetitive arrays of the rRNA genes, which code for the mature RNA components of ribosomes, flanked by intergenic spacer sequences (IGS) (Figure 1A). rDNA loci are considered to be one of the most unstable regions of the genome due to their repetitive nature and high transcriptional activity. The rDNA is highly transcribed even during S phase, leading to possible collisions between replication and transcription machineries. This collision can result in double strand breaks, further contributing to genomic instability of the rDNA (Helmrich et al, 2013; Takeuchi et al, 2003). RDNA instability (i.e. reduction of rDNA copy number and associated accumulation of ERCs) is a major cause of replicative aging/senescence (Ganley and Kobayashi, 2014; Kobayashi, 2011; Sinclair and Guarente, 1997). Despite clear involvement of the rDNA in the replicative lifespan of yeast, whether and how rDNA instability contributes to aging of multicellular organisms remains unclear. Despite the clear relationship between rDNA and aging, and that between aging and stem cells, little is known about whether or how the rDNA may change in stem cells during organismal aging
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