Cell fate in the <italic>C. elegans</italic> germline is regulated by the CPEB protein FOG -1.

Abstract

In <italic>C. elegans</italic>, sexual identity is determined by a cascade of sex-determination genes. Genetic epistasis tests indicate that <italic> fog-1</italic> acts at the end of this cascade in the germ line, and might directly control germ cell fates. I cloned the <italic>fog-1</italic> gene and found that it encodes an RNA-binding protein of the Cytoplasmic Polyadenylation Element Binding (CPEB) protein family. These proteins have been shown to regulate the translation of target messenger RNAs. Analyses of mutations show that the conserved RNA binding domains are essential for FOG-1 activity, since all known <italic>fog-1</italic> missense mutations are clustered in these domains. Furthermore, biochemical experiments show that FLAG-tagged FOG-1 binds to its own 3<super>'</super>-UTR <italic>in vitro</italic>. The interaction between FOG-1 and its 3<super>'</super> UTR seems to be specific, since mutant <italic>fog-1</italic> 3<super>'</super>-UTR competes poorly with the wild-type <italic>fog-1</italic> 3<super>' </super>-UTR for interaction with FOG-1. Based on those results, we hypothesize that FOG-1 might control germ cell fates by regulating the translation of its own and other messenger RNAs. FOG-1 is the first CPEB proteins known to be involved in spermatogenesis. To learn how FOG-1 acquired this activity, I cloned CPEB genes from related species of nematodes. I found that all of these species have four CPEB genes, and that the origin of these four types of CPEB proteins predates this group of nematodes. Furthermore, the function of FOG-1 has been conserved during nematode evolution. Finally, each FOG-1 contains a large, conserved insertion in one of the RNA-binding domains. Since the other nematode CPEB proteins groups also have their own unique insertions, these alterations might represent a general mechanism for altering CPEB protein function.