title: A C-terminal truncated mutation of spr-3 gene extends lifespan in Caenorhabditis elegans.
abstract: The lifespan of Caenorhabditis elegans is determined by various genetic and environmental factors. In this paper, spr-3, a C. elegans homologous gene of the mammalian neural restrictive silencing factor (NRSF/REST), is reported to be an important gene regulating lifespan of C. elegans. A deletion mutation of spr-3, spr-3(ok2525), or RNAi inhibition of spr-3 expression led to the short lifespan phenotype in C. elegans. However, a nonsense mutation of spr-3, spr-3(by108), increased the lifespan by 26% when compared with that of wild-type nematode. The spr-3(by108) also showed increased resistance to environmental stress. The spr-3(by108) mutated gene encodes a C-terminal truncated protein with a structure comparable with the REST4, a splice variant of the NRSF/REST in mammalian. The long lifespan phenotype of spr-3(by108) mutant is confirmed as a gain of function and dependent on normal functions of daf-16 and glp-1. The lifespan of the spr-3(by108) can be synergistically enhanced by inducing a mutation in daf-2. Quantitative polymerase chain reaction results showed that the expression of daf-16 as well as its target gene sod-3, mtl-1, and sip-1 was up-regulated in the spr-3(by108) mutant. These results would be helpful to further understand the complex function of NRSF/REST gene in mammalian, especially in the aging process and longevity determination.
authors.affiliation: School of Life Science and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Ruilin
authors.initials: R
authors.lastname: Sun
authors.forename: Minghui
authors.initials: M
authors.lastname: Yao
authors.forename: Weidong
authors.initials: W
authors.lastname: Chen
authors.forename: Zhugang
authors.initials: Z
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Fei
mesh_terms: D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics*; D017931:DNA Primers; D008136:Longevity / Q000235:genetics*; D009154:Mutation; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D012097:Repressor Proteins; C474656:SPR-3 protein, C elegans
keywords: NRSF/REST; daf-16; daf-2; lifespan; spr-3