rDNA array length is a major determinant of replicative lifespan in budding yeast.
rDNA array length is a major determinant of replicative lifespan in budding yeast.
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DOI：
10.1073/pnas.2119593119
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发表时间：
2022-04-12
影响因子：
11.1
通讯作者：
中科院分区：
文献类型：
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作者：
在真核基因组中，编码核糖体RNA(RDNA)的基因被组织成一个重复的阵列。这些基因的拷贝数经常变化，并对遗传和环境做出反应。在这里，我们证明了rDNA基因座拷贝数的变化能够改变酵母的复制寿命。这些结果表明，考虑rDNA拷贝数和可能改变这个动态染色体位点的条件，对于评估寿命是至关重要的。我们认为，这个rDNA基因座代表了真核基因组中一种重复的元件，它逃避了容易的检测，但具有表型后果，在这种情况下是寿命。调节衰老和决定寿命的复杂过程和相互作用对于任何生物体来说都没有完全定义。在这里，利用研究发芽酵母衰老的最新技术进步，我们发现了存在于其染色体阵列中的核糖体RNA基因的拷贝数与复制寿命(RLS)之间的一种以前未被认识到的关系。具体来说，染色体核糖体DNA(RDNA)拷贝数(RDNA CN)与RLS呈正相关，这种相互作用解释了一系列野生型菌株RLS变异的70%以上。在rDNA CN低的菌株中，Sir2的表达减弱，染色体外rDNA环(ERC)聚集增加，导致寿命缩短。通过缺失FOB1来抑制ERC的形成，消除了rDNA CN与RLS之间的关系。这些数据表明，先前发现的rDNA CN调节机制限制了寿命。重要的是，已报道的延长寿命突变的RLSS受到rDNA CN的显著影响，这表明rDNA CN的变化可能解释了一些已报道的影响的程度。我们认为，由于rDNA CN受环境、遗传和随机因素的调节，因此考虑rDNA CN是准确解释寿命数据的先决条件。
Genes encoding ribosomal RNA (rDNA) are organized into a repetitive array in eukaryotic genomes. The copy number of these genes often varies and is responsive to genetics and environment. Here, we show that variation in copy number at the rDNA locus is capable of altering replicative lifespan in yeast. These results indicate that considering rDNA copy number, and conditions that could potentially change this dynamic chromosome locus, is critical for evaluating lifespan. We propose that this rDNA locus represents the kind of repeated element in eukaryotic genomes that escapes easy detection, yet has phenotypic consequences, in this case lifespan. The complex processes and interactions that regulate aging and determine lifespan are not fully defined for any organism. Here, taking advantage of recent technological advances in studying aging in budding yeast, we discovered a previously unappreciated relationship between the number of copies of the ribosomal RNA gene present in its chromosomal array and replicative lifespan (RLS). Specifically, the chromosomal ribosomal DNA (rDNA) copy number (rDNA CN) positively correlated with RLS and this interaction explained over 70% of variability in RLS among a series of wild-type strains. In strains with low rDNA CN, SIR2 expression was attenuated and extrachromosomal rDNA circle (ERC) accumulation was increased, leading to shorter lifespan. Suppressing ERC formation by deletion of FOB1 eliminated the relationship between rDNA CN and RLS. These data suggest that previously identified rDNA CN regulatory mechanisms limit lifespan. Importantly, the RLSs of reported lifespan-enhancing mutations were significantly impacted by rDNA CN, suggesting that changes in rDNA CN might explain the magnitude of some of those reported effects. We propose that because rDNA CN is modulated by environmental, genetic, and stochastic factors, considering rDNA CN is a prerequisite for accurate interpretation of lifespan data.
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影响因子：
7.8
作者：
D'Aquila P;Montesanto A;Mandalà M;Garasto S;Mari V;Corsonello A;Bellizzi D;Passarino G
通讯作者：
Passarino G
影响因子：
4.5
作者：
Kruegel U;Robison B;Dange T;Kahlert G;Delaney JR;Kotireddy S;Tsuchiya M;Tsuchiyama S;Murakami CJ;Schleit J;Sutphin G;Carr D;Tar K;Dittmar G;Kaeberlein M;Kennedy BK;Schmidt M
通讯作者：
Schmidt M
影响因子：
64.5
作者：
Gottschling DE;Nyström T
通讯作者：
Nyström T
DOI：
10.1126/science.aaf7040
发表时间：
2016-07-29
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Holland ML;Lowe R;Caton PW;Gemma C;Carbajosa G;Danson AF;Carpenter AA;Loche E;Ozanne SE;Rakyan VK
通讯作者：
Rakyan VK
影响因子：
46.9
作者：
通讯作者：
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