Targeted RNAi screen reveals novel regulators of RNA-binding protein phase transitions in Caenorhabditis elegans oocytes.

The ability of oocytes to maintain their quality is essential for successful reproduction. One critical aspect of oocyte quality and successful embryogenesis after fertilization is the proper regulation of the stores of maternal mRNA by RNA-binding proteins. Many RNA-binding proteins undergo regulated phase transitions during oogenesis, and alterations of the protein phase can disrupt its ability to regulate mRNA stability and translation. In Caenorhabditis elegans, regulators of RNA-binding protein phase transitions in maturing oocytes of young adult hermaphrodites remain poorly characterized. However, a few recently identified genes are also required for the clearance of damaged proteins during maturation, suggesting coordination between these processes. To explore this relationship and gain insight into the regulation of phase transitions, we conducted a targeted RNAi screen of genes required for removal of protein aggregates in maturing oocytes. Here, we identify 6 novel regulators of phase transitions of the KH-domain protein MEX-3. We present strong evidence that the regulation of MEX-3 phase transitions in the oocyte overlaps with, but is distinct from, the regulatory network of protein aggregate clearance.