Molecular alterations during larval development of Haemonchus contortus in vitro are under tight post-transcriptional control

Molecular alterations during larval development of Haemonchus contortus in vitro are under tight post-transcriptional control
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DOI:
10.1016/j.ijpara.2018.03.008
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发表时间:
2018-08-01
影响因子:
4
通讯作者:
Gasser, Robin B.
Gasser, Robin B.
中科院分区:
医学2区
文献类型:
--
作者:
Ma, Guangxu;Wang, Tao;Gasser, Robin B.

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在这项研究中,我们探讨了分子变化的发育开关从L3到脱鞘L3(xL 3)和L4阶段的捻转血矛线虫在体外使用集成的转录组学,蛋白质组学和生物信息学的方法。共鉴定出9,754种mRNA、88种microRNA(miRNAs)和1,591种蛋白质,在研究的所有幼虫阶段推断出6,686种miRNA-mRNA对。约16%的转录本在组合的转录组(代表所有三个幼虫阶段)表达为蛋白质,并有正相关(r = 0.39-0.44)之间的mRNA转录和蛋白质表达的寄生虫的三个不同的发展阶段。在预测的靶标中,1,019个(27.0%)mRNA转录物表达为蛋白质,并且在成对比较时,发育阶段之间的差异mRNA转录和蛋白质表达存在负相关(r = -0.60至-0.50)。从自由生活到寄生生活史阶段的转录(mRNA和miRNA)和蛋白质表达的变化。与代谢相关的生物途径中的富集有关的扭转(例如,碳水化合物和脂质降解,以及氨基酸代谢),环境信息处理(例如,信号转导、信号分子和相互作用)和/或遗传信息处理(例如,转录和翻译)。具体而言,脂肪酸降解,类固醇激素的生物合成和Rap 1信号通路被抑制,而转录,翻译和蛋白质加工在内质网上调期间从自由生活的L3到寄生xL 3和L4阶段的线虫在体外的过渡。显性转录后调节被推断为引起这些变化,并且特定的miRNA(例如,hco-miR-34和hco-miR-252)似乎在H.扭曲两者合计,这些综合结果提供了一个全面的了解这种重要的寄生虫在体外分子水平的发育生物学。这里的方法适用于H。捻转线虫可以容易地应用于其它寄生线虫。(C)2018年澳大利亚寄生虫学会。由爱思唯尔有限公司出版。保留所有权利。
In this study, we explored the molecular alterations in the developmental switch from the L3 to the exsheathed L3 (xL3) and to the L4 stage of Haemonchus contortus in vitro using an integrated transcriptomic, proteomic and bioinformatic approach. Totals of 9,754 mRNAs, 88 microRNAs (miRNAs) and 1,591 proteins were identified, and 6,686 miRNA-mRNA pairs inferred in all larval stages studied. Approximately 16% of transcripts in the combined transcriptome (representing all three larval stages) were expressed as proteins, and there were positive correlations (r = 0.39-0.44) between mRNA transcription and protein expression in the three distinct developmental stages of the parasite. Of the predicted targets, 1,019 (27.0%) mRNA transcripts were expressed as proteins, and there was a negative correlation (r = -0.60 to -0.50) in the differential mRNA transcription and protein expression between developmental stages upon pairwise comparison. The changes in transcription (mRNA and miRNA) and protein expression from the free-living to the parasitic life cycle phase of H. contortus related to enrichments in biological pathways associated with metabolism (e.g., carbohydrate and lipid degradation, and amino acid metabolism), environmental information processing (e.g., signal transduction, signalling molecules and interactions) and/or genetic information processing (e.g., transcription and translation). Specifically, fatty acid degradation, steroid hormone biosynthesis and the Rap1 signalling pathway were suppressed, whereas transcription, translation and protein processing in the endoplasmic reticulum were upregulated during the transition from the free-living L3 to the parasitic xL3 and L4 stages of the nematode in vitro. Dominant post-transcriptional regulation was inferred to elicit these changes, and particular miRNAs (e.g., hco-miR-34 and hco-miR-252) appear to play roles in stress responses and/or environmental adaptations during developmental transitions of H. contortus. Taken together, these integrated results provide a comprehensive insight into the developmental biology of this important parasite at the molecular level in vitro. The approach applied here to H. contortus can be readily applied to other parasitic nematodes. (C) 2018 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.