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

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Title: The de novo design and synthesis of yeast chromosome XIII facilitates investigations on aging
Authors: 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
Source: Nat Commun
Nature Communications, Vol 15, Iss 1, Pp 1-12 (2024)
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, vol. 15, no. 1, pp. 10139. https://doi.org/10.1038/s41467-024-54130-3
Publisher Information: Springer Science and Business Media LLC, 2024.
Publication Year: 2024
Subject Terms: 0301 basic medicine, Aging, Saccharomyces cerevisiae Proteins, Science, Saccharomyces cerevisiae, Chromosomes, Article, Saccharomyces cerevisiae/genetics, 03 medical and health sciences, Gene Expression Regulation, Fungal, Aging/genetics, Transcription Factors/metabolism, Chromosomes, Artificial, Yeast, 0303 health sciences, Chromosomes, Fungal/genetics, Fungal/genetics, Chromosomes, Artificial, Yeast/genetics, Gene Expression Profiling, Fungal, Gene Expression Regulation, Synthetic Biology/methods, Artificial, Yeast/genetics, Saccharomyces cerevisiae Proteins/genetics, Synthetic Biology, Chromosomes, Fungal, Transcription Factors
Description: 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.
Document Type: Article
Other literature type
Language: English
ISSN: 2041-1723
DOI: 10.1038/s41467-024-54130-3
Access URL: https://pubmed.ncbi.nlm.nih.gov/39578428
https://doaj.org/article/60d909e6a81a4fc18ff20ea86b0148a3
https://research.manchester.ac.uk/en/publications/51d25cfa-2995-47e2-b532-8831e8a98c1c
https://doi.org/10.1038/s41467-024-54130-3
Rights: CC BY NC ND
Accession Number: edsair.doi.dedup.....9718528a00d9e41a19bcb86fd39ca2bc
Database: OpenAIRE
Description
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.
ISSN:20411723
DOI:10.1038/s41467-024-54130-3