RT Journal Article
SR Electronic
T1 Spt4 drives cellular senescence by activating non-coding RNA transcription in ribosomal RNA gene clusters
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.04.22.488906
DO 10.1101/2022.04.22.488906
A1 Masaaki Yokoyama
A1 Mariko Sasaki
A1 Takehiko Kobayashi
YR 2022
UL http://biorxiv.org/content/early/2022/04/22/2022.04.22.488906.abstract
AB Genome instability can drive aging in many organisms. The ribosomal RNA gene (rDNA) cluster is one of the most unstable regions in the genome. Replicative lifespan in budding yeast is correlated to rDNA stability, suggesting that the rDNA locus produces an aging signal. To understand the underlying mechanism, we looked for yeast mutants with more stable rDNA and longer lifespan than wild-type cells. We reveal that absence of a transcription elongation factor, Spt4, resulted in an increased rDNA stability, a reduced activity of the regulatory E-pro promoter in the rDNA, and extended replicative lifespan in a SIR2-dependent manner. Spt4-dependent lifespan restriction was abolished in the absence of non-coding RNA transcription at the E-pro locus. The amount of Spt4 increases and its function becomes more important as cells age. These findings suggest that Spt4 is a promising aging factor that accelerates cellular senescence through rDNA instability driven by non-coding RNA transcriptionCompeting Interest StatementThe authors have declared no competing interest.