Functional analysis of microRNA activity in Brugia malayi

Liu, Canhui; Voronin, Denis; Poole, Catherine B.; Bachu, Saheed; Rogers, Matthew B.; Jin, Jingmin; Ghedin, Elodie; Lustigman, Sara; McReynolds, Larry A.; Unnasch, Thomas R.

doi:10.1016/j.ijpara.2015.04.004

Cited by 6 publications

(5 citation statements)

References 25 publications

(36 reference statements)

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“…Tool development in B. malayi has been enabled by the range of DNA transformation techniques available: microinjection in adult females ( Higazi et al 2002 ), bombardment of adult females and embryos ( Higazi et al 2002 ), and calcium phosphate precipitate-mediated transformation of L3 larvae in cell culture media ex vivo or in jird peritonea in vivo ( Xu et al 2011 ). Available tools include: (i) immunofluorescence ( Landmann et al 2012 ); (ii) secreted Gaussia luciferase ( Xu et al 2011 ) and nonsecreted firefly and Renilla luciferase reporters ( Liu et al 2010 ), which can be used to study various aspects of gene expression, including miRNA control ( Liu et al 2015 ); and (iii) RNAi ex vivo on adult females to interrogate embryo gene function ( Aboobaker and Blaxter 2003 ; Landmann et al 2012 ), on L3 larvae ex vivo ( Kushwaha et al 2012 ), and in vivo in the mosquito vector to target L2 and L3 larvae ( Song et al 2010 ). It is important to note that in many parasitic nematodes, including Brugia spp., RNAi efficacy is extremely variable, with robust knockdown only observed for a limited number of genes ( Geldhof et al 2006 ; Maule et al 2011 ; Dalzell et al 2012 ).…”

Section: Existing Technologies In Parasitesmentioning

confidence: 99%

Rendering the Intractable More Tractable: Tools from Caenorhabditis elegans Ripe for Import into Parasitic Nematodes

Ward

2015

Genetics

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Recent and rapid advances in genetic and molecular tools have brought spectacular tractability to Caenorhabditis elegans, a model that was initially prized because of its simple design and ease of imaging. C. elegans has long been a powerful model in biomedical research, and tools such as RNAi and the CRISPR/Cas9 system allow facile knockdown of genes and genome editing, respectively. These developments have created an additional opportunity to tackle one of the most debilitating burdens on global health and food security: parasitic nematodes. I review how development of nonparasitic nematodes as genetic models informs efforts to import tools into parasitic nematodes. Current tools in three commonly studied parasites (Strongyloides spp., Brugia malayi, and Ascaris suum) are described, as are tools from C. elegans that are ripe for adaptation and the benefits and barriers to doing so. These tools will enable dissection of a huge array of questions that have been all but completely impenetrable to date, allowing investigation into host–parasite and parasite–vector interactions, and the genetic basis of parasitism.

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Section: Existing Technologies In Parasitesmentioning

confidence: 99%

Rendering the Intractable More Tractable: Tools from Caenorhabditis elegans Ripe for Import into Parasitic Nematodes

Ward

2015

Genetics

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“…miR-71 is also necessary for survival of primary cells in E. multilocularis, and oogenesis in L. migratoria ( Lucanic et al, 2013 ; Finger et al, 2019 ; Pérez et al, 2019 ; Song et al, 2019 ). It is additionally present in the roundworm Brugia malayi , and is involved in helminth parasitism ( Liu C. et al, 2015 ; Rojas-Pirela et al, 2022 ). Ets1 is a highly evolutionarily conserved transcription factor, which in vertebrates is involved in development of melanocytes and the coronary vascular endothelium, as well as organ formation from mesodermal cells ( Kola et al, 1993 ; Saldana-Caboverde et al, 2015 ; Wang et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Transcription of microRNAs is regulated by developmental signaling pathways and transcription factors

Arnott,

Sampilo,

Song

2024

Front. Cell Dev. Biol.

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In early embryonic development, the cross-regulation of transcription factors and signaling pathways are critical in mediating developmental and physiological processes. Additionally, many studies have shown the importance of post-transcriptional regulation of signaling and network components mediated by microRNAs (miRNAs); however, how miRNAs are transcriptionally regulated is poorly understood. miRNAs are critical fine-tuners of many biological processes and their dysregulation leads to a variety of diseases and developmental defects. Previously, we have shown that miRNAs are dynamically expressed throughout sea urchin development, suggesting that miRNAs are likely to be under transcriptional regulation. Here, we used pharmacological inhibitors, genetic constructs, and loss-of-function reagents to assess the impact of key signaling pathways (Wnt, Nodal, MAPK, Sonic Hedgehog, Delta/Notch, VEGF, and BMP) and transcription factors (Alx1, Ets1/2, and Tbr) on the transcript levels of the evolutionarily conserved miR-1, miR-31, miR-92 and miR-124; the invertebrate-specific miR-71; and the echinoderm-specific miR-2002, miR-2007, and miR-2012. We also used computational methods to identify potential transcription factor binding sites of these miRNAs. Lists of binding motifs for transcription factors (TFs) were acquired from the MEME-Suite Motif Database and used as inputs for the algorithm FIMO (Find Individual Motif Occurrences), which detects short nucleotide motifs within larger sequences. Based on experimental data on miRNA expression in conjunction with bioinformatic predictions, we propose that the transcription factors Tbr, Alx1, and Ets1 regulate SpmiR-1, SpmiR-31, and SpmiR-71, respectively. We additionally observed significant effects on miRNA levels as a result of perturbations to Wnt, Nodal, MAPK, and Sonic Hedgehog signaling pathways, while no significant change on miRNA levels were observed with perturbations to Delta/Notch, VEGF, or BMP signaling pathways. Overall, this study provides insights into the transcriptional regulation of miRNAs by signaling pathways and transcription factors and contribute to our overall understanding of the genetic regulation of developmental processes.

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“…The regulation of longevity by both signaling pathways allows Mf to circulate throughout the host body for a long time until a mosquito ingests it. In addition, the expression of ammonium transport protein and proteins involved in the Lin-12/Notch signaling pathway have also been proposed as targets of bma-miR-71 in B. malayi [ 155 ].…”

Section: Mirna In Brugia Malayi –Host Interactionmentioning

confidence: 99%

microRNAs: Critical Players during Helminth Infections

et al. 2022

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MicroRNAs (miRNAs) are a group of small non-coding RNAs that regulate gene expression post-transcriptionally through their interaction with the 3′ untranslated regions (3′ UTR) of target mRNAs, affecting their stability and/or translation. Therefore, miRNAs regulate biological processes such as signal transduction, cell death, autophagy, metabolism, development, cellular proliferation, and differentiation. Dysregulated expression of microRNAs is associated with infectious diseases, where miRNAs modulate important aspects of the parasite–host interaction. Helminths are parasitic worms that cause various neglected tropical diseases affecting millions worldwide. These parasites have sophisticated mechanisms that give them a surprising immunomodulatory capacity favoring parasite persistence and establishment of infection. In this review, we analyze miRNAs in infections caused by helminths, emphasizing their role in immune regulation and its implication in diagnosis, prognosis, and the development of therapeutic strategies.

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Functional analysis of microRNA activity in Brugia malayi

Cited by 6 publications

References 25 publications

Rendering the Intractable More Tractable: Tools from Caenorhabditis elegans Ripe for Import into Parasitic Nematodes

Rendering the Intractable More Tractable: Tools from Caenorhabditis elegans Ripe for Import into Parasitic Nematodes

Transcription of microRNAs is regulated by developmental signaling pathways and transcription factors

microRNAs: Critical Players during Helminth Infections

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