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Acidic growth conditions stabilize the ribosomal RNA gene cluster and extend lifespan through noncoding transcription repression
Genes to Cells ( IF 2.1 ) Pub Date : 2023-12-08 , DOI: 10.1111/gtc.13089
Yo Hasegawa 1, 2 , Hiroyuki Ooka 1, 2 , Tsuyoshi Wakatsuki 1, 2, 3 , Mariko Sasaki 1 , Ayumi Yamamoto 4 , Takehiko Kobayashi 1, 2, 3, 5
Affiliation  

Blackcurrant (Ribes nigrum L.) is a classical fruit that has long been used to make juice, jam, and liqueur. Blackcurrant extract is known to relieve cells from DNA damage caused by hydrogen peroxide (H2O2), methyl methane sulfonate (MMS), and ultraviolet (UV) radiation. We found that blackcurrant extract (BCE) stabilizes the ribosomal RNA gene cluster (rDNA), one of the most unstable regions in the genome, through repression of noncoding transcription in the intergenic spacer (IGS) which extended the lifespan in budding yeast. Reduced formation of extrachromosomal circles (ERCs) after exposure to fractionated BCE suggested that acidity of the growth medium impacted rDNA stability. Indeed, alteration of the acidity of the growth medium to pH ~4.5 by adding HCl increased rDNA stability and extended the lifespan. We identified RPD3 as the gene responsible for this change, which was mediated by the RPD3L histone deacetylase complex. In mammals, as inflammation sites in a tissue are acidic, DNA maintenance may be similarly regulated to prevent genome instability from causing cancer.

中文翻译:

酸性生长条件可稳定核糖体 RNA 基因簇并通过非编码转录抑制延长寿命

黑醋栗(Ribes nigrum L.)是一种经典水果,长期以来被用来制作果汁、果酱和利口酒。众所周知,黑加仑提取物可以缓解细胞免受过氧化氢 (H 2 O 2 )、甲基磺酸甲酯 (MMS) 和紫外线 (UV) 辐射引起的 DNA 损伤。我们发现黑加仑提取物 (BCE) 通过抑制基因间间隔区 (IGS) 中的非编码转录来稳定核糖体 RNA 基因簇 (rDNA),这是基因组中最不稳定的区域之一,从而延长了芽殖酵母的寿命。暴露于分级的 BCE 后染色体外环 (ERC) 的形成减少表明生长培养基的酸度影响 rDNA 稳定性。事实上,通过添加 HCl 将生长培养基的酸度更改为 pH ~4.5 可提高 rDNA 稳定性并延长寿命。我们确定RPD3是导致这种变化的基因,这种变化是由 RPD3L 组蛋白脱乙酰酶复合物介导的。在哺乳动物中,由于组织中的炎症部位呈酸性,DNA 的维持可能会受到类似的调节,以防止基因组不稳定导致癌症。
更新日期:2023-12-08
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