ROP-1, an RNA quality-control pathway component, affectsCaenorhabditis elegansdauer formation

Abstract

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.Ro ribonucleoprotein complex ͉ aspartic proteinase ͉ ribosome biogenesis ͉ 5S rRNA ͉ daf-2 T he dauer pathway is a specialized stress-resistant, alternative developmental stage of the nematode Caenorhabditis elegans (for review, see ref. 1). Developing worms are prone to form dauer larvae when environmental conditions become unfavorable for growth and reproduction. To make this developmental decision, the worms integrate a variety of sensory information about environmental conditions, including the density of conspecific animals, food availability, and temperature (2, 3). When growth conditions improve, dauer larvae can exit the dauer stage and resume normal development. The subsequent life history parameters of adult animals who passed through the dauer stage, such as brood size and life span, are independent of the time spent as dauer larva. The worm monitors external conditions to determine whether it is favorable to enter the dauer stage rather than to proceed along the normal developmental program, but it is currently not known whether internal conditions, such as previously sustained molecular damage, are also monitored.A complex cascade of genetic interactions regulates entry into the dauer stage, and at least three pathways have been defined: daf-2, daf-7, and daf-11. The daf-2 gene encodes an insulin...

A role for a bacterial ortholog of the Ro autoantigen in starvation-induced rRNA degradation

“…Consistent with this role, the 3′ ends of misfolded pre-5S RNAs insert through the X. laevis Ro central cavity (12), and the fate of these RNAs is to be degraded (10). Moreover, animal cell Ro proteins, like Rsr, are part of the response to several forms of environmental stress (11,14,15). Although eukaryotic Ro proteins have not been described to be upregulated during stress, the accumulation of Ro in nuclei that occurs after UV irradiation and oxidative stress (11,14) may increase the effective Ro concentration, thus facilitating interaction with nuclear RNA targets and protein partners.…”

“…Moreover, after UV irradiation and in oxidative stress, the normally cytoplasmic Ro accumulates in nuclei (11,14). Caenorhabditis elegans lacking the Ro ortholog rop-1 fail to form dauer larvae, a stress response to starvation (15). How the quality control function of Ro relates to its role in stress responses is unknown.…”

A conserved motif of vertebrate Y RNAs essential for chromosomal DNA replication

“…Functions for Ro60 have been implicated in cellular responses to cytotoxic stress (Labbe et al 2000;Chen et al 2003), in a quality control for small RNAs (Chen and Wolin 2004;Stein et al 2005;Fuchs et al 2006;Chen et al 2007;Hogg and Collins 2007), the export of associated RNAs from the nucleus (Simons et al 1996), and the protection of associated RNAs from exonucleolytic degradation (Chen and Wolin 2004). In vertebrates, the binding site for Ro60 is adjacent to the domain essential for DNA replication, and thus insulates it from the 59 and 39 ends of the RNA.…”

A lupus-like syndrome develops in mice lacking the Ro 60-kDa protein, a major lupus autoantigen

“…C. elegans lacking the Ro protein are defective in the formation of dauer larvae, a stress-resistant stage formed when environmental conditions are unfavorable for growth (16). D. radiodurans lacking the Ro protein exhibit decreased survival after UV irradiation.…”