A systematic RNAi screen for longevity genes in C-elegans

A systematic RNAi screen for longevity genes in C-elegans
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DOI:
10.1101/gad.1308205
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发表时间:
2005-07-01
影响因子:
10.5
通讯作者:
Lee, SS
Lee, SS
中科院分区:
生物学1区
文献类型:
--
作者:
Hamilton, B;Doug, YQ;Lee, SS

文献摘要

被引文献

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我们在这里报告了长寿基因的第一个全基因组功能基因组筛选。采用大规模RNA干扰(RNAi)技术对秀丽隐杆线虫基因进行了系统分析,发现89个基因的RNAi失活可延长秀丽隐杆线虫的寿命。daf-2/胰岛素样信号通路的组成部分,以及调节代谢、信号转导、蛋白质转换和基因表达的基因被恢复。许多这些候选长寿基因在动物系统发育中是保守的。与新的长寿基因的遗传相互作用分析表明,一些基因在daf-16/FOXO转录因子或sir2.1蛋白去乙酰化酶的上游发挥作用,而其他基因则独立于daf-16/FOXO和sir2.1发挥作用,这可能定义了调节寿命的新途径。
We report here the first genome-wide functional genomic screen for longevity genes. We systematically surveyed Caenorhabditis elegans genes using large-scale RNA interference (RNAi), and found that RNAi inactivation of 89 genes extend C. elegans lifespan. Components of the daf-2/insulin-like signaling pathway are recovered, as well as genes that regulate metabolism, signal transduction, protein turnover, and gene expression. Many of these candidate longevity genes are conserved across animal phylogeny. Genetic interaction analyses with the new longevity genes indicate that some act upstream of the daf-16/FOXO transcription factor or the sir2.1 protein deacetylase, and others function independently of daf-16/FOXO and sir2.1, and might define new pathways to regulate lifespan.