Biology Department, Siena College, Loudonville, NY 12211, USA.
Int J Mol Sci. 2024 Oct 1;25(19):10593. doi: 10.3390/ijms251910593.
Retrotransposons are mobile DNA elements that are more active with increasing age and exacerbate aging phenotypes in multiple species. We previously reported an unexpected extension of chronological lifespan in the yeast, , due to the presence of Ty1 retrotransposons when cells were aged under conditions of mild stress. In this study, we tested a subset of genes identified by RNA-seq to be differentially expressed in strains with a high-copy number of Ty1 retrotransposons compared with a strain with no retrotransposons and additional candidate genes for their contribution to lifespan extension when cells were exposed to a moderate dose of hydroxyurea (HU). Deletion of , , or prevented lifespan extension, while deletion of , , or partially prevented lifespan extension. Genes overexpressed in high-copy Ty1 strains did not typically have Ty1 insertions in their promoter regions. We found that silencing genomic copies of Ty1 prevented lifespan extension, while expression of Ty1 from a high-copy plasmid extended lifespan in medium with HU or synthetic medium. These results indicate that cells adapt to expression of retrotransposons by changing gene expression in a manner that can better prepare them to remain healthy under mild stress.
逆转录转座子是一种移动的 DNA 元件，随着年龄的增长而变得更加活跃，并在多种物种中加剧衰老表型。我们之前报道过，由于在轻度应激条件下老化时细胞中存在 Ty1 逆转录转座子，酵母的生理时钟寿命会意外延长。在这项研究中，我们测试了一组通过 RNA-seq 鉴定的基因，这些基因在 Ty1 逆转录转座子高拷贝数的菌株中与没有逆转录转座子的菌株相比，其表达水平存在差异，并进一步测试了候选基因在细胞暴露于中等剂量羟基脲 (HU) 时对寿命延长的贡献。 缺失 、 或 阻止了寿命的延长，而缺失 、 或 部分阻止了寿命的延长。在高拷贝 Ty1 菌株中高表达的基因通常在其启动子区域没有 Ty1 插入。我们发现，沉默 Ty1 的基因组拷贝数可以防止寿命延长，而在含有 HU 或合成培养基的培养基中，高拷贝质粒表达 Ty1 则延长了寿命。这些结果表明，细胞通过改变基因表达的方式来适应逆转录转座子的表达，从而更好地准备在轻度应激下保持健康。
