Screening and characterization of aging regulators using synthesized yeast chromosomeXIII

Author:

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

Abstract

AbstractYeast, a single eukaryotic cell model organism, demonstrates a progressive aging process. In the era of synthetic biology, study of the impact of synthetic chromosomes and aging is urgent and intriguing. Herein, we successfully constructed the 884 KbsynXIIIofSaccharomyces cerevisiaeand conducted replicative aging studies using the synthetic strains. We verified that the rRNA-related transcriptional factorRRN9is a major positive controller of replicative lifespan. Using SCRaMbLE and anHSP104reporter as a biomarker for mutant discovery, we screened 135 SCRaMbLEd synXIII strains with extended lifespan and identified 10 genes onsynXIIIthat potentially serve as aging regulators. In addition, the genome-scale regression analysis of long-replicative lifespan SCRaMbLEd strains revealed distinct dysregulation of nucleus, ribosome, and mitochondrion function networks. Our findings suggest that Sc2.0 yeast has potential for unveiling new aging-related genes and gene-gene interactions underlying replicative lifespan.

Publisher

Cold Spring Harbor Laboratory

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