Differential expression of microRNAs and tRNA fragments mediate the adaptation of the liver fluke Fasciola gigantica to its intermediate snail and definitive mammalian hosts

Hu, Rui-Si; Zhang, Xiaoxuan; Ma, Qiao-Ni; Elsheikha, Hany M.; Ehsan, Muhammad; Zhao, Quan; Fromm, Bastian; Zhu, Xingquan

doi:10.1016/j.ijpara.2020.10.009

Cited by 15 publications

(27 citation statements)

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“…At present the miRNome of F. hepatica is composed of 34 conserved families (13 of them with more than one miRNA within the family). An almost identical complement of miRNAs was recently reported in F. gigantica (Hu et al, 2021) and previously in S. mansoni (Ovchinnikov et al, 2020) (summarized in Figure 2A), FIGURE 1 | Mapping of small RNA sequences from different stages of Fasciola hepatica to the genome. Samples were obtained from metacercaria (MC), newly excysted juvenile (NEJ) adult worms (AD), and adult-released extracellular vesicles (EVs).…”

Section: Mirna Profiles Vary Greatly Between Different Stagessupporting

confidence: 77%

“…indicating that these losses could have been in the origin of the adaptation to parasitism of the clade. In addition, to the conserved miRNA, 15 novel F. hepatica exclusive miRNAs have been described previously (Ricafrente et al, 2021), four of which were also confirmed in the miRNA complement of F. gigantica (Hu et al, 2021). Here, we further extended the Fasciola specific miRNome by adding nine new well supported miRNAs (fhe-miR-NEW-1 to 9 in Figure 2 and Figure S3), with seven of them, also predicted to be conserved in the F. gigantica genome (Table S2).…”

Section: Mirna Profiles Vary Greatly Between Different Stagesmentioning

confidence: 70%

“…miRNAs conserved across Lophotrochozoans and Flatworms showed low expression in all samples, despite significant variations for fhe-miR-1992, fhe-miR-1989 and fhe-miR-3479. However, when we compared our results with those described in the sister species F. gigantica (Hu et al, 2021), we noticed that several lophotrochozoan and flatworm conserved miRNAs (e.g. miR-1992, miR-1989, miR-2160-P1 & -P2, and miR-11584), showed higher expression in egg and the intra-snail stages (Figure S5).…”

Section: Mirna Profiles Vary Greatly Between Different Stagesmentioning

confidence: 85%

“…Since then, miRNAs have been described in all eukaryotes (Wheeler et al, 2009;Tarver et al, 2013) and perform varied functional roles including cellular differentiation, apoptosis, metabolism and silencing of transposable elements (Bushati and Cohen, 2007;Tristań-Ramos et al, 2020). MiRNAs have also been described in several platyhelminths (Palakodeti et al, 2006;Basika et al, 2016;Cai et al, 2016;Stroehlein et al, 2018), including the NEJ and adult stages of F. hepatica (Xu et al, 2012;Fontenla et al, 2015;Fromm et al, 2015) and more recently in eight stages of the life cycle of F. gigantica (Hu et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

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Role of Fasciola hepatica Small RNAs in the Interaction With the Mammalian Host

Fontenla

Langleib

Torre-Escudero

et al. 2022

Front. Cell. Infect. Microbiol.

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MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression being involved in many different biological processes and play a key role in developmental timing. Additionally, recent studies have shown that miRNAs released from parasites are capable of regulating the expression of host genes. In the present work, we studied the expression patterns of ncRNAs of various intra-mammalian life-cycle stages of the liver fluke, Fasciola hepatica, as well as those packaged into extracellular vesicles and shed by the adult fluke. The miRNA expression profile of the intra-mammalian stages shows important variations, despite a set of predominant miRNAs that are highly expressed across all stages. No substantial variations in miRNA expression between dormant and activated metacercariae were detected, suggesting that they might not be central players in regulating fluke gene expression during this crucial step in the invasion of the definitive host. We generated a curated pipeline for the prediction of putative target genes that reports only sites conserved between three different prediction approaches. This pipeline was tested against an iso-seq curated database of the 3’ UTR regions of F. hepatica genes to detect miRNA regulation networks within liver fluke. Several functions related to the host immune response or modulation were enriched among the targets of the most highly expressed parasite miRNAs, stressing that they might be key players during the establishment and maintenance of infection. Additionally, we detected fragments derived from the processing of tRNAs, in all developmental stages analyzed, and documented the presence of novel long tRNA fragments enriched in vesicles. We confirmed the presence of at least 5 putative vault RNAs (vtRNAs), that are expressed across different stages and enriched in vesicles. The presence of tRNA fragments and vtRNAs in vesicles raise the possibility that they could be involved in the host-parasite interaction.

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Section: Mirna Profiles Vary Greatly Between Different Stagessupporting

confidence: 77%

Section: Mirna Profiles Vary Greatly Between Different Stagesmentioning

confidence: 70%

Section: Mirna Profiles Vary Greatly Between Different Stagesmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Role of Fasciola hepatica Small RNAs in the Interaction With the Mammalian Host

Fontenla

Langleib

Torre-Escudero

et al. 2022

Front. Cell. Infect. Microbiol.

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“…A recent study on F. gigantica (Hu et al, 2021) measured miRNA expression across intra-mammalian and intra-molluscan life stages, linking these sequences with regulation of metabolism, transport, growth and development. Given the miRNA homology shared between F. hepatica and F. gigantica (Hu et al, 2021) this dataset is a useful comparative tool that could yield insights for F. hepatica as well. F. hepatica secretes miRNAs, which are of interest given their potential role in host-parasite interactions and as diagnostic biomarkers.…”

Section: Introductionmentioning

confidence: 99%

Developmental regulation and functional prediction of microRNAs in an expanded Fasciola hepatica miRNome

Herron

O’Connor

Robb

et al. 2021

Preprint

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1ABSTRACTThe liver fluke, Fasciola hepatica, is a global burden on the wellbeing and productivity of farmed ruminants, and a zoonotic threat to human health. Despite the clear need for accelerated discovery of new drug and vaccine treatments for this pathogen, we still have a relatively limited understanding of liver fluke biology and host interactions. Noncoding RNAs, including micro (mi)RNAs, are key to transcriptional regulation in all eukaryotes, such that an understanding of miRNA biology can shed light on organismal function at a systems level. Four previous publications have reported up to 89 mature miRNA sequences from F. hepatica, but our data show that this does not represent a full account of this species miRNome. We have expanded on previous studies by sequencing, for the first time, miRNAs from multiple life stages (adult, newly excysted juvenile (NEJ), metacercariae and adult-derived extracellular vesicles (EVs)). These experiments detected an additional 61 high-confidence miRNAs, most of which have not been described in any other species, expanding the F. hepatica miRNome to 150 mature sequences. We used quantitative (q)PCR assays to provide the first developmental profile of miRNA expression across metacercariae, NEJ, adult and adult-derived Evs. The majority of miRNAs were expressed most highly in metacercariae, with at least six distinct expression clusters apparent across life stages. Intracellular miRNAs were functionally analysed to identify target mRNAs with inversely correlated expression in F. hepatica tissue transcriptomes, highlighting regulatory interactions with key virulence transcripts including cathepsin proteases, and neuromuscular genes that control parasite growth, development and motility. We also linked 28 adult-derived EV miRNAs with downregulation of 397 host genes in F. hepatica-infected transcriptomes from ruminant lymph node, peripheral blood mononuclear cell (PBMC) and liver tissue transcriptomes. These included genes involved in signal transduction, immune and metabolic pathways, adding to the evidence for miRNA-based immunosuppression during fasciolosis. These data expand our understanding of the F. hepatica miRNome, provide the first data on developmental miRNA regulation in this species, and provide a set of testable hypotheses for functional genomics interrogations of liver fluke miRNA biology.CONTRIBUTION TO THE FIELDPrevious studies identified 89 micro (mi)RNAs (non-coding RNAs responsible for regulating gene expression) in the trematode parasite, Fasciola hepatica, and attached functional annotations to the miRNAs that are secreted by liver fluke in vitro. This study expands the known miRNA complement of F. hepatica by 40%, adding an additional 61 miRNAs, many of which appear Fasciola-specific. We used this expanded dataset to perform the first analysis of developmental miRNA expression across intra-mammalian parasites, showing clear developmentally regulated expression profiles across infectious metacercariae, juvenile and adult parasites, and extracellular vesicles secreted by adult parasites. We performed rigorous functional annotation of cellular miRNAs, correlating their expression with mRNA transcriptomes to identify potential roles for specific miRNAs in regulating expression of important proteases and nerve/muscle transcripts, all of which are important for parasite virulence. We also functionally analysed miRNAs secreted by adult parasites in terms of interactions with host transcripts; for the first time this analysis was supported by host transcriptome data, linking secreted miRNAs with mRNAs that are downregulated by fluke infection in sheep and cattle. This work contributes new data, insights and analyses to the field, providing a rich source of hypotheses for future experimental validation.

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One-health approach on the future application of snails: a focus on snail-transmitted parasitic diseases

Pathak,

Luitel,

Utaaker

et al. 2023

Parasitol Res

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Snails are fascinating molluscs with unique morphological and physiological adaptive features to cope with various environments. They have traditionally been utilized as food and feed sources in many regions of the world. The future exploitation of alternative nutrient sources, like snails, is likely to increase further. Snails, however, also serve as an intermediate host for several zoonotic parasites. A category of parasitic infections, known as snail-transmitted parasitic diseases (STPDs), is harmful to humans and animals and is mainly driven by various trematodes, cestodes, and nematodes. The environment plays a crucial role in transmitting these parasites, as suitable habitats and conditions can facilitate their growth and proliferation in snails. In light of diverse environmental settings and biologically categorized snail species, this review evaluates the dynamics of significant STPDs of zoological importance. Additionally, possible diagnostic approaches for the prevention of STPDs are highlighted. One-health measures must be considered when employing snails as an alternative food or feed source to ensure the safety of snail-based products and prevent any adverse effects on humans, animals, and the environment.

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Differential expression of microRNAs and tRNA fragments mediate the adaptation of the liver fluke Fasciola gigantica to its intermediate snail and definitive mammalian hosts

Cited by 15 publications

References 61 publications

Role of Fasciola hepatica Small RNAs in the Interaction With the Mammalian Host

Role of Fasciola hepatica Small RNAs in the Interaction With the Mammalian Host

Developmental regulation and functional prediction of microRNAs in an expanded Fasciola hepatica miRNome

One-health approach on the future application of snails: a focus on snail-transmitted parasitic diseases

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