The RING Finger Protein RNF1 Forms an Interaction Network with Regulators of Sexual Development.

RNA-binding E3 ubiquitin ligases (RBULs) provide a link between RNA metabolic processes and the ubiquitin proteasome system (UPS). In humans, RBULs are involved in various biological processes, such as cell proliferation and differentiation, as well as sexual development. To date, little is known about their role in the protozoan parasite , the causative agent of malaria tropica. We previously identified a novel RBUL, the RING finger E3 ligase RNF1, which is highly expressed during gametocyte development. Here, we conducted BioID-based proximity interaction studies to unveil the RNF1 interactome. We show that in immature gametocytes, RNF1 forms an interaction network that is mainly composed of RNA-binding proteins, including the translational repressors DOZI and CITH and members of the CCR4-NOT complex, as well as UPS-related proteins. In particular, RNF1 interacts with recently identified regulators of sexual development like the zinc finger protein MD3, with which it shares the majority of interactors. The common interactome of RNF1 and MD3 comprises several uncharacterized proteins predominantly expressed in male or female gametocytes. Our results demonstrate that RNF1 engages with RNA-binding proteins crucial for sex determination in gametocytes, thereby linking posttranscriptional regulation with the UPS.