The de novo design and synthesis of yeast chromosome XIII facilitates investigations on aging

IF 14.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2024-11-22 DOI:10.1038/s41467-024-54130-3

Chun Zhou, Yun Wang, Yikun Huang, Yongpan An, Xian Fu, Daqian Yang, Yilin Wang, Jintao Zhang, Leslie A. Mitchell, Joel S. Bader, Yizhi Cai, Junbiao Dai, Jef D. Boeke, Zhiming Cai, Zhengwei Xie, Yue Shen, Weiren Huang

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Abstract

In the era of synthetic biology, design, construction, and utilization of synthetic chromosomes with unique features provide a strategy to study complex cellular processes such as aging. Herein, we successfully construct the 884 Kb synXIII of Saccharomyces cerevisiae to investigate replicative aging using these synthetic strains. We verify that up-regulation of a rRNA-related transcriptional factor, RRN9, positively influence replicative lifespan. Using SCRaMbLE system that enables inducible whole-genome rearrangement on synXIII, we obtain 20 SCRaMbLEd synXIII strains with extended lifespan. Transcriptome analysis reveal the expression of genes involve in global protein synthesis is up-regulated in longer-lived strains. We establish causal links between genotypic change and the long-lived phenotype via reconstruction of some key structural variations observed in post-SCRaMbLE strains and further demonstrate combinatorial effects of multiple aging regulators on lifespan extension. Our findings underscore the potential of synthetic yeasts in unveiling the function of aging-related genes.

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酵母 XIII 染色体的全新设计与合成有助于研究衰老问题

在合成生物学时代，设计、构建和利用具有独特特征的合成染色体为研究衰老等复杂的细胞过程提供了一种策略。在本文中，我们成功构建了 884 Kb 的酿酒酵母 synXIII，并利用这些合成菌株研究了复制衰老。我们验证了rRNA相关转录因子RRN9的上调会对复制寿命产生积极影响。利用SCRaMbLE系统对synXIII进行诱导性全基因组重排，我们获得了20株具有延长寿命的SCRaMbLEd synXIII菌株。转录组分析表明，在寿命较长的菌株中，参与全局蛋白质合成的基因表达上调。我们通过重建在后SCRaMbLE菌株中观察到的一些关键结构变异，建立了基因型变化与长寿表型之间的因果联系，并进一步证明了多种衰老调节因子对寿命延长的组合效应。我们的发现强调了合成酵母在揭示衰老相关基因功能方面的潜力。

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.