体内接触吡喹酮后曼氏血吸虫体内长非编码 RNA 水平的变化

IF 3.6 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Non-Coding RNA Pub Date : 2024-04-19 DOI:10.3390/ncrna10020027
Pedro Jardim Poli, Agatha Fischer-Carvalho, A. Tahira, John D. Chan, S. Verjovski-Almeida, Murilo Sena Amaral
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引用次数: 0

摘要

血吸虫病是一种由血吸虫属吸虫引起的疾病,影响着全球 2 亿多人。几十年来,吡喹酮 (PZQ) 一直是治疗这种疾病的唯一药物。尽管最近发现了瞬时受体离子通道是 PZQ 的靶点,但血吸虫对这种药物的反应仍不完全清楚,因为药效取决于其他因素,而这些因素可能会引发寄生虫基因表达的复杂调控。长非编码 RNA(lncRNA)是指长度超过 200 个核苷酸的转录本,其蛋白质编码潜能较低或没有,在曼氏血吸虫的平衡、繁殖和生育中发挥重要作用。在这里,我们发现体内 PZQ 处理可调节曼氏沙门氏菌的 lncRNA 水平。我们重新分析了经 PZQ 体内处理的成熟和未成熟曼森氏杆菌蠕虫的公开 RNA-Seq 数据,检测到数百个 lncRNA 在药物暴露后有差异表达,其中许多在成熟和未成熟蠕虫中共享。有趣的是,我们发现这些lncRNA并不是成虫阶段特异性的,它们与PZQ调控的蛋白编码基因共同表达。通过证明寄生虫 lncRNA 的表达水平会随着对 PZQ 的反应而改变,这项研究为阐明曼氏沙门氏菌对 PZQ 反应的复杂机制迈出了重要的一步。
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Long Non-Coding RNA Levels Are Modulated in Schistosoma mansoni following In Vivo Praziquantel Exposure.
Schistosomiasis is a disease caused by trematodes of the genus Schistosoma 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 S. mansoni homeostasis, reproduction, and fertility. Here, we show that in vivo PZQ treatment modulates lncRNA levels in S. mansoni. We re-analyzed public RNA-Seq data from mature and immature S. mansoni worms treated in vivo 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 S. mansoni response to PZQ.
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来源期刊
Non-Coding RNA
Non-Coding RNA Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
6.70
自引率
4.70%
发文量
74
审稿时长
10 weeks
期刊介绍: Functional studies dealing with identification, structure-function relationships or biological activity of: small regulatory RNAs (miRNAs, siRNAs and piRNAs) associated with the RNA interference pathway small nuclear RNAs, small nucleolar and tRNAs derived small RNAs other types of small RNAs, such as those associated with splice junctions and transcription start sites long non-coding RNAs, including antisense RNAs, long ''intergenic'' RNAs, intronic RNAs and ''enhancer'' RNAs other classes of RNAs such as vault RNAs, scaRNAs, circular RNAs, 7SL RNAs, telomeric and centromeric RNAs regulatory functions of mRNAs and UTR-derived RNAs catalytic and allosteric (riboswitch) RNAs viral, transposon and repeat-derived RNAs bacterial regulatory RNAs, including CRISPR RNAS Analysis of RNA processing, RNA binding proteins, RNA signaling and RNA interaction pathways: DICER AGO, PIWI and PIWI-like proteins other classes of RNA binding and RNA transport proteins RNA interactions with chromatin-modifying complexes RNA interactions with DNA and other RNAs the role of RNA in the formation and function of specialized subnuclear organelles and other aspects of cell biology intercellular and intergenerational RNA signaling RNA processing structure-function relationships in RNA complexes RNA analyses, informatics, tools and technologies: transcriptomic analyses and technologies development of tools and technologies for RNA biology and therapeutics Translational studies involving long and short non-coding RNAs: identification of biomarkers development of new therapies involving microRNAs and other ncRNAs clinical studies involving microRNAs and other ncRNAs.
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