Farrukh Afia, Musa Sherihan, Distler Ute, Tenzer Stefan, Pradel Gabriele, Ngwa Che Julius
Division of Cellular and Applied Infection Biology, RWTH Aachen University, 52074 Aachen, Germany.
Institute of Immunology, University Medical Centre of the Johannes-Gutenberg University, 55131 Mainz, Germany.
Int J Mol Sci. 2025 Jun 7;26(12):5470. doi: 10.3390/ijms26125470.
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.
RNA结合E3泛素连接酶（RBULs）在RNA代谢过程与泛素蛋白酶体系统（UPS）之间建立了联系。在人类中，RBULs参与多种生物学过程，如细胞增殖和分化以及性发育。迄今为止，人们对它们在热带疟原虫（疟疾的病原体）中的作用知之甚少。我们之前鉴定出一种新型RBUL，即环状结构域E3连接酶RNF1，它在配子体发育过程中高度表达。在此，我们进行了基于BioID的邻近相互作用研究以揭示RNF1相互作用组。我们发现，在未成熟配子体中，RNF1形成一个主要由RNA结合蛋白组成的相互作用网络，包括翻译抑制因子DOZI和CITH以及CCR4-NOT复合物成员，还有与UPS相关的蛋白。特别地，RNF1与最近鉴定出的性发育调节因子如锌指蛋白MD3相互作用，它们共享大部分相互作用蛋白。RNF1和MD3的共同相互作用组包含几种主要在雄配子体或雌配子体中表达的未表征蛋白。我们的结果表明，RNF1与配子体性别决定中至关重要的RNA结合蛋白相互作用，从而将转录后调控与UPS联系起来。
