Jardim Poli Pedro, Fischer-Carvalho Agatha, Tahira Ana Carolina, Chan John D, Verjovski-Almeida Sergio, Sena Amaral Murilo
Laboratório de Ciclo Celular, Instituto Butantan, São Paulo 05503-900, SP, Brazil.
Global Health Institute, University of Wisconsin-Madison, Madison, WI 53792, USA.
Noncoding RNA. 2024 Apr 19;10(2):27. doi: 10.3390/ncrna10020027.
Schistosomiasis is a disease caused by trematodes of the genus that affects over 200 million people worldwide. For decades, praziquantel (PZQ) has been the only available drug to treat the disease. Despite recent discoveries that identified a transient receptor ion channel as the target of PZQ, schistosome response to this drug remains incompletely understood, since effectiveness relies on other factors that may trigger a complex regulation of parasite gene expression. Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with low or no protein-coding potential that play important roles in homeostasis, reproduction, and fertility. Here, we show that PZQ treatment modulates lncRNA levels in . We re-analyzed public RNA-Seq data from mature and immature worms treated with PZQ and detected hundreds of lncRNAs differentially expressed following drug exposure, many of which are shared among mature and immature worms. Through RT-qPCR, seven out of ten selected lncRNAs were validated as differentially expressed; interestingly, we show that these lncRNAs are not adult worm stage-specific and are co-expressed with PZQ-modulated protein-coding genes. By demonstrating that parasite lncRNA expression levels alter in response to PZQ, this study unravels an important step toward elucidating the complex mechanisms of response to PZQ.
血吸虫病是一种由血吸虫属吸虫引起的疾病，全球有超过2亿人受其影响。几十年来，吡喹酮一直是治疗该疾病的唯一可用药物。尽管最近发现一种瞬时受体离子通道是吡喹酮的靶点，但血吸虫对这种药物的反应仍未完全了解，因为其有效性依赖于其他可能触发寄生虫基因表达复杂调控的因素。长链非编码RNA（lncRNA）是长度超过200个核苷酸且蛋白质编码潜能低或无的转录本，在体内平衡、繁殖和生育中发挥重要作用。在此，我们表明吡喹酮处理可调节血吸虫中的lncRNA水平。我们重新分析了来自用吡喹酮处理的成熟和未成熟血吸虫的公开RNA测序数据，并检测到数百种在药物暴露后差异表达的lncRNA，其中许多在成熟和未成熟血吸虫中都有。通过逆转录定量PCR，所选的十种lncRNA中有七种被验证为差异表达；有趣的是，我们表明这些lncRNA并非成虫阶段特异性的，并且与吡喹酮调节的蛋白质编码基因共表达。通过证明寄生虫lncRNA表达水平因吡喹酮而改变，本研究为阐明血吸虫对吡喹酮反应的复杂机制迈出了重要一步。
