An RNA binding polymer specifies nematode sperm fate

Metazoan gamete development into sperm or oocytes requires specific programming cues. Many of these cues function through conserved proteins to regulate gene expression. In C. elegans, two proteins are the terminal regulators of the genetic regulatory network controlling sperm fate: FOG-1, a cytoplasmic polyadenylation element binding protein (CPEB), and FOG-3, a predicted Tob/BTG protein. Loss of either gene causes hermaphrodites or male germ cells to switch from making sperm to making oocytes. Characterized Tob/BTG proteins function as adaptor proteins, linking – in certain contexts – deadenylases to mRNA via CPEB RNA motifs. Through crosslinking and sequencing, we confirmed FOG-3 binds to RNA directly and observed a preference for mRNA 3'UTRs. Our results bring together prior genetics and molecular biology data to propose a new molecular function in germ cell specification with a Tob protein. We discuss the potential for FOG-3 to function as an mRNA packaging protein to inhibit target genes, as well as the potential for the existence of other hidden protein polymers in biology. Overall design: iCLIP was performed on 4 biological replicates of C. elegans L4 larvae expressing FLAG-tagged FOG-3 integrated into the genome. 4 biological replicates of control samples comprised the same worms processed by an identical protocol, except that the immunopurification did not include the antibody for the FLAG epitope, and, as a result, did not specifically purify FOG-3.