Labbé J C, Burgess J, Rokeach L A, Hekimi S
Biology Department, McGill University, 1205 Dr. Penfield Avenue, Montréal, QC H3A 1B1, Canada.
Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13233-8. doi: 10.1073/pnas.230284297.
Caenorhabditis elegans dauer formation is an alternative larval developmental pathway that the worm can take when environmental conditions become detrimental. Animals can survive several months in this stress-resistant stage and can resume normal development when growth conditions improve. Although the worms integrate a variety of sensory information to commit to dauer formation, it is currently unknown whether they also monitor internal cellular damage. The Ro ribonucleoprotein complex, which was initially described as a human autoantigen, is composed of one major 60-kDa protein, Ro60, that binds to one of four small RNA molecules, designated Y RNAs. Ro60 has been shown to bind mutant 5S rRNA molecules in Xenopus oocytes, suggesting a role for Ro60 in 5S rRNA biogenesis. Analysis of ribosomes from a C. elegans rop-1(-) strain, which is null for the expression of Ro60, demonstrated that they contain a high percentage of mutant 5S rRNA molecules, thereby strengthening the notion of a link between the rop-1 gene product and 5S rRNA quality control. The Ro particle was recently shown to be involved in the resistance of Deinococcus radiodurans to UV irradiation, suggesting a role for the Ro complex in stress resistance. We have studied the role of rop-1 in dauer formation. We present genetic and biochemical evidence that rop-1 interacts with dauer-formation genes and is involved in the regulation of the worms' entry into the dauer stage. Furthermore, we find that the rop-1 gene product undergoes a proteolytic processing step that is regulated by the dauer formation pathway via an aspartic proteinase. These results suggest that the Ro particle may function in an RNA quality-control checkpoint for dauer formation.
秀丽隐杆线虫滞育形成是一种替代幼虫发育途径,当环境条件变得不利时,线虫可以采取这种途径。动物可以在这个抗逆阶段存活数月,并在生长条件改善时恢复正常发育。尽管线虫整合了各种感官信息以决定进入滞育形成阶段,但目前尚不清楚它们是否也监测内部细胞损伤。Ro核糖核蛋白复合体最初被描述为一种人类自身抗原,由一种主要的60 kDa蛋白Ro60组成,Ro60与四种小RNA分子之一(称为Y RNA)结合。已证明Ro60在非洲爪蟾卵母细胞中与突变型5S rRNA分子结合,这表明Ro60在5S rRNA生物合成中发挥作用。对秀丽隐杆线虫rop-1(-)菌株(该菌株中Ro60表达缺失)的核糖体分析表明,它们含有高比例的突变型5S rRNA分子,从而强化了rop-1基因产物与5S rRNA质量控制之间存在联系的观点。最近发现Ro颗粒参与了耐辐射球菌对紫外线照射的抗性,这表明Ro复合体在抗逆中发挥作用。我们研究了rop-1在滞育形成中的作用。我们提供了遗传和生化证据,表明rop-1与滞育形成基因相互作用,并参与调控线虫进入滞育阶段。此外,我们发现rop-1基因产物经历了一个蛋白水解加工步骤,该步骤由滞育形成途径通过一种天冬氨酸蛋白酶进行调控。这些结果表明,Ro颗粒可能在滞育形成的RNA质量控制检查点中发挥作用。