TY - JOUR
T1 - The de novo design and synthesis of yeast chromosome XIII facilitates investigations on aging
AU - Zhou, Chun
AU - Wang, Yun
AU - Huang, Yikun
AU - An, Yongpan
AU - Fu, Xian
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
N1 - © 2024. The Author(s).
PY - 2024/11/22
Y1 - 2024/11/22
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.
AB - 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.
KW - Saccharomyces cerevisiae/genetics
KW - Saccharomyces cerevisiae Proteins/genetics
KW - Gene Expression Regulation, Fungal
KW - Chromosomes, Fungal/genetics
KW - Synthetic Biology/methods
KW - Transcription Factors/metabolism
KW - Gene Expression Profiling
KW - Chromosomes, Artificial, Yeast/genetics
KW - Aging/genetics
U2 - 10.1038/s41467-024-54130-3
DO - 10.1038/s41467-024-54130-3
M3 - Article
C2 - 39578428
SN - 2041-1723
VL - 15
SP - 10139
JO - Nature Communications
JF - Nature Communications
IS - 1
ER -