Cherkasova V, Ayyadevara S, Egilmez N, Shmookler Reis R
Departments of Geriatrics, Medicine, and Biochemistry & Molecular Biology, University of Arkansas for Medical Sciences, and Central Arkansas Veterans Health Care System - Research 151, 4300 West 7th Street, Little Rock, AR, 72205, USA.
J Mol Biol. 2000 Jul 14;300(3):433-48. doi: 10.1006/jmbi.2000.3880.
Under adverse conditions, the nematode Caenorhabditis elegans undergoes reversible developmental arrest as dauer larvae, an alternative third larval stage adapted for dispersal and long-term survival. Following such arrest, which may exceed three times their usual life-span, worms resume development to form reproductive adults of normal subsequent longevity. Mutations of genes in the dauer-formation (daf) pathway can extend life-span two- to fourfold, even in adults that mature without diapause. To identify transcript-level changes that might contribute to extended survival, we prepared a subtractive cDNA library of messages more abundant in dauer than in non-dauer (L3) larvae. Six genes were confirmed as three- to ninefold upregulated in dauer larvae, after correction for mRNA load: genes encoding poly(A)-binding protein (PABP), heat-shock proteins hsp70 and hsp90, and three novel genes of uncertain function. The novel genes encode a partial homologue of human activating signal cointegrator 1 (ASC-1), a GTP-binding homologue of a ribosomal protein, and an SH3-domain protein. Transcript levels for all except hsp70 increased during aging in two C. elegans strains, whereas the three novel genes (and possibly PABP) were also induced to varying degrees by starvation of adults. All six genes are expressed at higher levels in young adults of long-lived daf mutant strains than in normal-longevity controls, suggesting that increased expression of these genes may play a protective function, thus favoring survival in diverse contexts.
在不利条件下,线虫秀丽隐杆线虫会以 dauer 幼虫的形式经历可逆的发育停滞,dauer 幼虫是适应扩散和长期生存的另一种第三幼虫阶段。经历这种可能超过其正常寿命三倍的停滞之后,线虫恢复发育,形成具有正常后续寿命的生殖成虫。即使在没有滞育而成熟的成虫中,dauer 形成(daf)途径中的基因突变也能使寿命延长两到四倍。为了确定可能有助于延长生存期的转录水平变化,我们制备了一个消减 cDNA 文库,该文库包含在 dauer 幼虫中比在非 dauer(L3)幼虫中更丰富的信息。在对 mRNA 负载进行校正后,六个基因被确认为在 dauer 幼虫中上调了三到九倍:编码多聚(A)结合蛋白(PABP)、热休克蛋白 hsp70 和 hsp90 的基因,以及三个功能未知的新基因。这些新基因编码人类激活信号共整合因子 1(ASC-1)的部分同源物、一种核糖体蛋白的 GTP 结合同源物和一种 SH3 结构域蛋白。除 hsp70 外,所有基因的转录水平在两种秀丽隐杆线虫品系的衰老过程中都有所增加,而这三个新基因(可能还有 PABP)也在成虫饥饿时受到不同程度的诱导。所有六个基因在长寿 daf 突变品系的年轻成虫中的表达水平都高于正常寿命的对照品系,这表明这些基因表达的增加可能起到保护作用,从而有利于在各种情况下生存。