Abstract
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, or sexual development. To date,
little is known about their role in the protozoan parasite
Plasmodium falciparum, the causative agent of malaria tropica. We
previously identified a first P. falciparum RBUL, the RING finger
E3 ligase PfRNF1, which is highly expressed during gametocyte
development. Here, we conducted BioID-based proximity interaction
studies to unveil the PfRNF1 interactome. We show that in
immature gametocytes PfRNF1 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, PfRNF1 interacts with
recently identified regulators of sexual development like the zinc
finger protein PfMD3, with which it shares the majority of
interactors. The common interactome of PfRNF1 and PfMD3
comprises several yet unknown proteins specifically expressed in male or
female gametocytes. Our results demonstrate that PfRNF1 engages
with RNA-binding proteins crucial for sex determination of gametocytes,
thereby linking posttranscriptional regulation with the ubiquitin
system.