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

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

doi:10.1038/s41467-024-54130-3

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

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

Biomedical Engineering

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	10139
Journal	Nature communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-54130-3
State	Published - Dec 2024

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Zhou, C., Wang, Y., Huang, Y., An, Y., Fu, X., Yang, D., Wang, Y., Zhang, J., Mitchell, L. A., Bader, J. S., Cai, Y., Dai, J., Boeke, J. D., Cai, Z., Xie, Z., Shen, Y., & Huang, W. (2024). The de novo design and synthesis of yeast chromosome XIII facilitates investigations on aging. Nature communications, 15(1), Article 10139. https://doi.org/10.1038/s41467-024-54130-3

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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.",

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

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doi = "10.1038/s41467-024-54130-3",

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AU - Zhou, Chun

AU - Wang, Yun

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AU - An, Yongpan

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AU - Yang, Daqian

AU - Wang, Yilin

AU - Zhang, Jintao

AU - Mitchell, Leslie A.

AU - Bader, Joel S.

AU - Cai, Yizhi

AU - Dai, Junbiao

AU - Boeke, Jef D.

AU - Cai, Zhiming

AU - Xie, Zhengwei

AU - Shen, Yue

AU - Huang, Weiren

PY - 2024/12

Y1 - 2024/12

N2 - 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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The de novo design and synthesis of yeast chromosome XIII facilitates investigations on aging

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