GLD-3 and control of the mitosis/meiosis decision in the germline of Caenorhabditis elegans

Germ cells can divide mitotically to replenish germline tissue or meiotically to produce gametes. In this article, we report that GLD-3, a Caenorhabditis elegans Bicaudal-C homolog, promotes the transition from mitosis to meiosis together with the GLD-2 poly(A) polymerase. GLD-3 binds GLD-2 via a small N-terminal region present in both GLD-3S and GLD-3L isoforms, and GLD-2 and GLD-3 can be co-immunoprecipitated from worm extracts. The FBF repressor binds specifically to elements in the gld-3S 3'-UTR, and FBF regulates gld-3 expression. Furthermore, FBF acts largely upstream of gld-3 in the mitosis/meiosis decision. By contrast, GLD-3 acts upstream of FBF in the sperm/oocyte decision, and GLD-3 protein can antagonize FBF binding to RNA regulatory elements. To address the relative importance of these two regulatory mechanisms in the mitosis/meiosis and sperm/oocyte decisions, we isolated a deletion mutant, gld-3(q741), that removes the FBF-binding site from GLD-3L, but leaves the GLD-2-binding site intact. Animals homozygous for gld-3(q741) enter meiosis, but are ferminized. Therefore, GLD-3 promotes meiosis primarily via its interaction with GLD-2, and it promotes spermatogenesis primarily via its interaction with FBF.