The Plasmodium falciparum RING Finger Protein PfRNF1 Forms an Interaction Network with Regulators of Sexual...

Area of Science:

• Molecular parasitology
• Ubiquitin-proteasome system
• RNA-binding proteins

Background:

• RNA-binding E3 ubiquitin ligases (RBULs) regulate crucial cellular processes by linking RNA metabolism and protein degradation.
• RBULs are implicated in human development, but their function in the malaria parasite *Plasmodium falciparum* remains largely unknown.
• A novel *P. falciparum* RBUL, *Pf*RNF1, is highly expressed during gametocyte development, suggesting a role in sexual reproduction.

Purpose of the Study:

• To investigate the molecular function of *Pf*RNF1 in *P. falciparum* gametocytes.
• To identify proteins interacting with *Pf*RNF1 using proximity-interaction studies.
• To elucidate the role of *Pf*RNF1 in linking RNA regulation and the ubiquitin-proteasome system during sexual development.

Main Methods:

• BioID-based proximity interaction studies were performed on immature *P. falciparum* gametocytes.
• Proteomic analysis was used to identify proteins in the *Pf*RNF1 interactome.
• Comparative analysis of interactomes for *Pf*RNF1 and *Pf*MD3 was conducted.

Main Results:

• *Pf*RNF1 forms an interaction network with RNA-binding proteins, including translational repressors (DOZI, CITH) and CCR4-NOT complex members.
• The *Pf*RNF1 interactome includes proteins involved in the ubiquitin-proteasome system (UPS).
• *Pf*RNF1 interacts with *Pf*MD3, a regulator of sexual development, sharing a significant number of interactors, including uncharacterized proteins specific to male or female gametocytes.

Conclusions:

• *Pf*RNF1 connects posttranscriptional regulation by RNA-binding proteins with the UPS in *P. falciparum* gametocytes.
• This interaction network is crucial for regulating sexual development and gametocyte maturation.
• The findings provide insights into the molecular mechanisms governing malaria parasite reproduction.