Minkler Sarah J, Loghry-Jansen Hannah J, Sondjaja Noelle A, Kimber Michael J
Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States.
Front Genet. 2022 May 31;13:884052. doi: 10.3389/fgene.2022.884052. eCollection 2022.
Circular RNAs (circRNAs) are a recently identified RNA species with emerging functional roles as microRNA (miRNA) and protein sponges, regulators of gene transcription and translation, and modulators of fundamental biological processes including immunoregulation. Relevant to this study, circRNAs have recently been described in the parasitic nematode, , suggesting they may have functionally important roles in parasites. Given their involvement in regulating biological processes, a better understanding of their role in parasites could be leveraged for future control efforts. Here, we report the use of next-generation sequencing to identify 1,997 distinct circRNAs expressed in adult female stages of the gastrointestinal parasitic nematode, We describe spatial expression in the ovary-enriched and body wall muscle, and also report circRNA presence in extracellular vesicles (EVs) secreted by the parasite into the external environment. Further, we used an approach to predict that a subset of circRNAs bind both endogenous parasite miRNAs as well as human host miRNAs, suggesting they could be functional as both endogenous and exogenous miRNA sponges to alter gene expression. There was not a strong correlation between circRNA length and endogenous miRNA interactions, indicating circRNAs are enriched for miRNA binding sites, but that human miRNAs were predicted form a more thermodynamically stable bond with circRNAs. These results suggest that secreted circRNAs could be interacting with host miRNAs at the host-parasite interface and influencing host gene transcription. Lastly, although we have previously found that therapeutically relevant concentrations of the anthelmintic drug ivermectin inhibited EV release from parasitic nematodes, we did not observe a direct effect of ivermectin treatment on circRNAs expression or secretion.
环状RNA（circRNAs）是最近发现的一种RNA，作为微小RNA（miRNA）和蛋白质海绵、基因转录和翻译的调节因子以及包括免疫调节在内的基本生物学过程的调节剂，发挥着越来越重要的功能作用。与本研究相关的是，最近在寄生线虫中描述了circRNAs，这表明它们可能在寄生虫中具有重要的功能作用。鉴于它们参与调节生物学过程，更好地了解它们在寄生虫中的作用可能有助于未来的控制工作。在这里，我们报告使用下一代测序技术在胃肠道寄生线虫的成年雌性阶段鉴定出1997种不同的circRNAs。我们描述了在富含卵巢和体壁肌肉中的空间表达，还报告了寄生虫分泌到外部环境中的细胞外囊泡（EVs）中存在circRNAs。此外，我们使用一种方法预测，一部分circRNAs既能结合内源性寄生虫miRNAs，也能结合人类宿主miRNAs，这表明它们可以作为内源性和外源性miRNA海绵来改变基因表达。circRNA长度与内源性miRNA相互作用之间没有很强的相关性，这表明circRNAs富含miRNA结合位点，但预测人类miRNAs与circRNAs形成的化学键在热力学上更稳定。这些结果表明，分泌的circRNAs可能在宿主 - 寄生虫界面与宿主miRNAs相互作用并影响宿主基因转录。最后，尽管我们之前发现治疗相关浓度的驱虫药伊维菌素抑制了寄生线虫的EV释放，但我们没有观察到伊维菌素处理对circRNAs表达或分泌有直接影响。
