Genome-Wide Transcriptome Analysis Reveals Extensive Alternative Splicing Events in the Protoscoleces of Echinococcus granulosus and Echinococcus multilocularis

Abstract

Alternative splicing (AS), as one of the most important topics in the post-genomic era, has been extensively studied in numerous organisms. However, little is known about the prevalence and characteristics of AS in Echinococcus species, which can cause significant health problems to humans and domestic animals. Based on high-throughput RNA-sequencing data, we performed a genome-wide survey of AS in two major pathogens of echinococcosis-Echinococcus granulosus and Echinococcus multilocularis. Our study revealed that the prevalence and characteristics of AS in protoscoleces of the two parasites were generally consistent with each other. A total of 6,826 AS events from 3,774 E. granulosus genes and 6,644 AS events from 3,611 E. multilocularis genes were identified in protoscolex transcriptomes, indicating that 33–36% of genes were subject to AS in the two parasites. Strikingly, intron retention instead of exon skipping was the predominant type of AS in Echinococcus species. Moreover, analysis of the Kyoto Encyclopedia of Genes and Genomes pathway indicated that genes that underwent AS events were significantly enriched in multiple pathways mainly related to metabolism (e.g., purine, fatty acid, galactose, and glycerolipid metabolism), signal transduction (e.g., Jak-STAT, VEGF, Notch, and GnRH signaling pathways), and genetic information processing (e.g., RNA transport and mRNA surveillance pathways). The landscape of AS obtained in this study will not only facilitate future investigations on transcriptome complexity and AS regulation during the life cycle of Echinococcus species, but also provide an invaluable resource for future functional and evolutionary studies of AS in platyhelminth parasites.

Identification of Functional MKK3/6 and MEK1/2 Homologs from Echinococcus granulosus and Investigation of Protoscolecidal Activity of Mitogen-Activated Protein Kinase Signaling Pathway Inhibitors In Vitro and In Vivo

“…Moreover, the biological activity of sorafenib tosylate may be due, in addition, to its actions against other targets (e.g., VEGFR, PDGFR, and Flt3) in this situation. However, according to recent studies, there are no known orthologs of VEGFR, PDGFR, or Flt3 expressed in Echinococcus spp., although the literature mentions the presence of a VEGF signaling pathway in E. multilocularis and E. granulosus (7,46). Therefore, at present, the parasiticidal effect of sorafenib tosylate could be only partially attributed to its inhibition of the MAPK pathway.…”

Bioinformatic analysis of a novel Echinococcus granulosus nuclear receptor with two DNA binding domains

“…On the one hand, considering that the synthesized cDNA represents the set of transcribed genes, it is possible that these receptors are not being transcribed in the larval stage of protoscoleces. On the other hand, it has been reported that in this larval stage, 33% of the genes are subject to alternative splicing, so it is also feasible that the genes corresponding to Eg2DBDβ and Eg2DBDγ undergo a process of this type in which case the primer hybridisation regions could be absent [43]. In this case, only Eg2DBDα isoform is expressed in protoscoleces.…”

Transcriptomic Features of Echinococcus granulosus Protoscolex during the Encystation Process

“…As such, it plays an important role in characterizing gene expression and regulation [11]. Whole-genome sequencing, proteomic analyses, and transcrip-tomic investigations have been used to identify the differentially expressed genes (DEGs) and proteins in the different life stages (adult, oncosphere, hydatid cyst, larval worms, and pepsin/H+-activated PSCs) of E. granulosus [12][13][14][15]. However, the transcriptomic features of PSCs in the encystation process have not yet been described.…”