酵母的衰老与染色体XII的扩增线性片段有关,而不是核糖体DNA圈的积累。

IF 7.8 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
PLoS Biology Pub Date : 2023-08-29 eCollection Date: 2023-08-01 DOI:10.1371/journal.pbio.3002250
Andre Zylstra, Hanane Hadj-Moussa, Dorottya Horkai, Alex J Whale, Baptiste Piguet, Jonathan Houseley
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引用次数: 1

摘要

长期以来,酵母母细胞中染色体外核糖体DNA圈(ERCs)的大量积累一直被认为是复制衰老的主要驱动因素。ERC是通过核糖体DNA(rDNA)重组产生的,大量遗传数据将导致ERC的rDNA不稳定事件与寿命缩短和其他衰老病理联系起来。然而,我们对ERC积累的分子效应知之甚少。在这里,我们研究了存在和不存在ERCs的情况下的衰老,出乎意料地发现没有证据表明基因表达差异可能表明ERCs引起的应激反应或代谢反馈。我们也没有观察到伴随酵母衰老的基因表达普遍中断的任何全球变化,这完全表明ERC在很大程度上是惰性的。酵母中伴随衰老的许多差异基因表达实际上与衰老进入点(SEP)的标志物有关,这表明衰老而不是衰老是这些变化的基础。细胞通过SEP而与ERC无关,但我们发现SEP与rDNA和端粒(ChrXIIr)之间的染色体XII区域的拷贝数扩增有关,形成高达约1.8Mb大小的线性片段,这是由于rDNA的不稳定性而在老化细胞中产生的,但其机制与ERC不同。因此,尽管由于ERC的积累,rDNA拷贝数随着年龄的增长而急剧增加,但我们的研究结果表明,在芽酵母衰老过程中,ChrXIIr而不是ERCs是衰老的主要驱动因素。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Senescence in yeast is associated with amplified linear fragments of chromosome XII rather than ribosomal DNA circle accumulation.

Senescence in yeast is associated with amplified linear fragments of chromosome XII rather than ribosomal DNA circle accumulation.

Senescence in yeast is associated with amplified linear fragments of chromosome XII rather than ribosomal DNA circle accumulation.

Senescence in yeast is associated with amplified linear fragments of chromosome XII rather than ribosomal DNA circle accumulation.

The massive accumulation of extrachromosomal ribosomal DNA circles (ERCs) in yeast mother cells has been long cited as the primary driver of replicative ageing. ERCs arise through ribosomal DNA (rDNA) recombination, and a wealth of genetic data connects rDNA instability events giving rise to ERCs with shortened life span and other ageing pathologies. However, we understand little about the molecular effects of ERC accumulation. Here, we studied ageing in the presence and absence of ERCs, and unexpectedly found no evidence of gene expression differences that might indicate stress responses or metabolic feedback caused by ERCs. Neither did we observe any global change in the widespread disruption of gene expression that accompanies yeast ageing, altogether suggesting that ERCs are largely inert. Much of the differential gene expression that accompanies ageing in yeast was actually associated with markers of the senescence entry point (SEP), showing that senescence, rather than age, underlies these changes. Cells passed the SEP irrespective of ERCs, but we found the SEP to be associated with copy number amplification of a region of chromosome XII between the rDNA and the telomere (ChrXIIr) forming linear fragments up to approximately 1.8 Mb size, which arise in aged cells due to rDNA instability but through a different mechanism to ERCs. Therefore, although rDNA copy number increases dramatically with age due to ERC accumulation, our findings implicate ChrXIIr, rather than ERCs, as the primary driver of senescence during budding yeast ageing.

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来源期刊
PLoS Biology
PLoS Biology 生物-生化与分子生物学
CiteScore
14.40
自引率
2.00%
发文量
359
审稿时长
3 months
期刊介绍: PLOS Biology is an open-access, peer-reviewed general biology journal published by PLOS, a nonprofit organization of scientists and physicians dedicated to making the world's scientific and medical literature freely accessible. The journal publishes new articles online weekly, with issues compiled and published monthly. ISSN Numbers: eISSN: 1545-7885 ISSN: 1544-9173
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