We are interested in understanding how cells become polarized and divide asymmetrically. In the early C. elegans embryo, the establishment and maintenance of cell polarity depend on the activity of the PAR proteins. Previous work demonstrated that while removing both copies of
par-2 leads to the mislocalization of the PAR-3 complex to the posterior of the embryo, and thus to defects in polarity and embryonic lethality, reducing by half the amounts of the PAR-3 complex protein PAR-6 in a
par-2 mutant background is sufficient to restore viability [Watts et al. (1996). Development 122: 3133-3140]. This indicates that genes involved in regulating the levels, the localization and/or the activity of PAR-3 complex components can be identified based on their ability to restore embryonic viability in a
par-2 mutant background. We have used an RNAi-based, genome-wide screening approach to find suppressors of
par-2(
it5ts) lethality and identified 11 novel components that participate in the C. elegans PAR polarity pathway. Most of these novel proteins are present in other species, suggesting that their role in cell polarity might also be conserved. One of these suppressors is encoded by
nos-3, one of the three C. elegans homologues of the Drosophila gene nanos. NOS-3 was previously shown to function with the Pumilio homologues FBF-1 and FBF-2 in the repression of
fem-3 mRNA translation in the germline. We found that removal of both
fbf-1 and
fbf-2 activity by RNAi can suppress
par-2(
it5ts). This suggests that NOS-3 functions, at least in part, to regulate the translation of a component in the PAR pathway. Analysis of time-lapse images of early development indicated that most of the early phenotypes associated with
par-2(lf) are efficiently suppressed in
nos-3(
q650);
par-2(
it5ts) mutant embryos. Furthermore, genetic analysis demonstrated that deletion of
nos-3(
q650) can suppress the null allele
par-2(
lw32), indicating that it impinges on the PAR pathway independently of the PAR-2 protein. Consistent with this, we found that the levels of the PAR-6 protein are lower in embryonic extracts from
nos-3(
q650) mutants. Some of the other suppressors identified, for instance the proteasome subunit encoding gene
rpn-10, do not suppress strong alleles of
par-2, suggesting that they might function via PAR-2 itself. Taken together, our results define novel components that regulate PAR protein function and uncover a novel role for Nanos in PAR protein-dependent cell polarity.