NANOS-3 and FBF proteins physically interact to control the sperm-oocyte switch in Caenorhabditis elegans

Background: The Caenorhabditis elegans FBF protein and its Drosophila relat ive, Pumilio, define a large family of eukaryotic RNA-binding proteins. By binding regulatory elements in the 3' untranslated regions (UTRs) of their cognate RNAs, FBF and Pumilio have key post-transcriptional roles in early developmental decisions. In C. elegans, FBF is required for repression of f em-3 mRNA to achieve the hermaphrodite switch from spermatogenesis to oogen esis. Results: We report here that FBF and NANOS-3 (NOS-3), one of three C. elega ns Nanos homologs, interact with each other in both yeast two-hybrid and in vitro assays. We have delineated the portions of each protein required for this interaction. Worms lacking nanos function were derived either by RNA- mediated interference (nos-1 and nos-2) or by use of a deletion mutant (nos -3). The roles of the three nos genes overlap during germ-line development. In certain nos-deficient animals, the hermaphrodite sperm-oocyte switch wa s defective, leading to the production of excess sperm and no oocytes. In o ther nos-deficient animals, the entire germ line died during larval develop ment. This germ-line death did not require CED-3, a protease required for a poptosis. Conclusions: The data suggest that NOS-3 participates in the sperm-oocyte s witch through its physical interaction with FBF, forming a regulatory compl ex that controls fem-3 mRNA. NOS-1 and NOS-2 also function in the switch, b ut do not interact directly with FBF. The three C. elegans nanos genes, lik e Drosophila nanos, are also critical for germ-line survival. We propose th at this may have been the primitive function of nanos genes.