RNAi screening of uncharacterized genes identifies promising druggable targets in Schistosoma japonicum

作者：Yuxiang Xie, Xiaoling Wang, Shaoyun Cheng, Wan‐Ling Liu, Cun Yi, Yanmin You, Wei Zhang, Yuepeng Wang, Enlu Tang, Jipeng Wang, Wei Hu · 发表于：PLoS Pathogens · 年份：2025 · DOI：10.1371/journal.ppat.1013014 · 被引用次数：9 · 研究领域：Parasites and Host Interactions、Trace Elements in Health、Research on Leishmaniasis Studies

Schistosomiasis affects more than 250 million people worldwide and is one of the neglected tropical diseases. Currently, the treatment of schistosomiasis relies on a single drug-praziquantel-which has led to increasing pressure from drug resistance. Therefore, there is an urgent need to find new treatments. The development of genome sequencing has provided valuable information for understanding the biology of schistosomes. In the genome of Schistosoma japonicum, approximately 11% of the protein-coding sequences are uncharacterized genes (UGs) annotated as "hypothetical protein" or "protein of unknown function." These poorly understood genes have been unjustifiably neglected, although some may be essential for the survival of the parasites and serve as potential drug targets. In this study, we systematically mined the highly expressed UGs in both genders of this parasite throughout key developmental stages in their mammalian host, using our previously published S. japonicum genome and RNA-seq data. By employing in vitro RNA interference (RNAi), we screened 126 UGs that lack homologs in Homo sapiens and identified 8 that are essential for the parasite vitality. We further investigated two UGs, Sjc_0002003 and Sjc_0009272, which resulted in the most severe phenotypes. Fluorescence in situ hybridization demonstrated that both genes were expressed throughout the body without sex bias. Silencing either Sjc_0002003 or Sjc_0009272 reduced the cell proliferation in the body. Furthermo...