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A novel member of the let-7 microRNA family is associated with developmental transitions in filarial nematode parasites

BACKGROUND: Filarial nematodes are important pathogens in the tropics transmitted to humans via the bite of blood sucking arthropod vectors. The molecular mechanisms underpinning survival and differentiation of these parasites following transmission are poorly understood. microRNAs are small non-cod...

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Autores principales: Winter, Alan D, Gillan, Victoria, Maitland, Kirsty, Emes, Richard D, Roberts, Brett, McCormack, Gillian, Weir, William, Protasio, Anna V, Holroyd, Nancy, Berriman, Matthew, Britton, Collette, Devaney, Eileen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4428239/
https://www.ncbi.nlm.nih.gov/pubmed/25896062
http://dx.doi.org/10.1186/s12864-015-1536-y
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author Winter, Alan D
Gillan, Victoria
Maitland, Kirsty
Emes, Richard D
Roberts, Brett
McCormack, Gillian
Weir, William
Protasio, Anna V
Holroyd, Nancy
Berriman, Matthew
Britton, Collette
Devaney, Eileen
author_facet Winter, Alan D
Gillan, Victoria
Maitland, Kirsty
Emes, Richard D
Roberts, Brett
McCormack, Gillian
Weir, William
Protasio, Anna V
Holroyd, Nancy
Berriman, Matthew
Britton, Collette
Devaney, Eileen
author_sort Winter, Alan D
collection PubMed
description BACKGROUND: Filarial nematodes are important pathogens in the tropics transmitted to humans via the bite of blood sucking arthropod vectors. The molecular mechanisms underpinning survival and differentiation of these parasites following transmission are poorly understood. microRNAs are small non-coding RNA molecules that regulate target mRNAs and we set out to investigate whether they play a role in the infection event. RESULTS: microRNAs differentially expressed during the early post-infective stages of Brugia pahangi L3 were identified by microarray analysis. One of these, bpa-miR-5364, was selected for further study as it is upregulated ~12-fold at 24 hours post-infection, is specific to clade III nematodes, and is a novel member of the let-7 family, which are known to have key developmental functions in the free-living nematode Caenorhabditis elegans. Predicted mRNA targets of bpa-miR-5364 were identified using bioinformatics and comparative genomics approaches that relied on the conservation of miR-5364 binding sites in the orthologous mRNAs of other filarial nematodes. Finally, we confirmed the interaction between bpa-miR-5364 and three of its predicted targets using a dual luciferase assay. CONCLUSIONS: These data provide new insight into the molecular mechanisms underpinning the transmission of third stage larvae of filarial nematodes from vector to mammal. This study is the first to identify parasitic nematode mRNAs that are verified targets of specific microRNAs and demonstrates that post-transcriptional control of gene expression via stage-specific expression of microRNAs may be important in the success of filarial infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1536-y) contains supplementary material, which is available to authorized users.
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spelling pubmed-44282392015-05-13 A novel member of the let-7 microRNA family is associated with developmental transitions in filarial nematode parasites Winter, Alan D Gillan, Victoria Maitland, Kirsty Emes, Richard D Roberts, Brett McCormack, Gillian Weir, William Protasio, Anna V Holroyd, Nancy Berriman, Matthew Britton, Collette Devaney, Eileen BMC Genomics Research Article BACKGROUND: Filarial nematodes are important pathogens in the tropics transmitted to humans via the bite of blood sucking arthropod vectors. The molecular mechanisms underpinning survival and differentiation of these parasites following transmission are poorly understood. microRNAs are small non-coding RNA molecules that regulate target mRNAs and we set out to investigate whether they play a role in the infection event. RESULTS: microRNAs differentially expressed during the early post-infective stages of Brugia pahangi L3 were identified by microarray analysis. One of these, bpa-miR-5364, was selected for further study as it is upregulated ~12-fold at 24 hours post-infection, is specific to clade III nematodes, and is a novel member of the let-7 family, which are known to have key developmental functions in the free-living nematode Caenorhabditis elegans. Predicted mRNA targets of bpa-miR-5364 were identified using bioinformatics and comparative genomics approaches that relied on the conservation of miR-5364 binding sites in the orthologous mRNAs of other filarial nematodes. Finally, we confirmed the interaction between bpa-miR-5364 and three of its predicted targets using a dual luciferase assay. CONCLUSIONS: These data provide new insight into the molecular mechanisms underpinning the transmission of third stage larvae of filarial nematodes from vector to mammal. This study is the first to identify parasitic nematode mRNAs that are verified targets of specific microRNAs and demonstrates that post-transcriptional control of gene expression via stage-specific expression of microRNAs may be important in the success of filarial infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1536-y) contains supplementary material, which is available to authorized users. BioMed Central 2015-04-22 /pmc/articles/PMC4428239/ /pubmed/25896062 http://dx.doi.org/10.1186/s12864-015-1536-y Text en © Winter et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Winter, Alan D
Gillan, Victoria
Maitland, Kirsty
Emes, Richard D
Roberts, Brett
McCormack, Gillian
Weir, William
Protasio, Anna V
Holroyd, Nancy
Berriman, Matthew
Britton, Collette
Devaney, Eileen
A novel member of the let-7 microRNA family is associated with developmental transitions in filarial nematode parasites
title A novel member of the let-7 microRNA family is associated with developmental transitions in filarial nematode parasites
title_full A novel member of the let-7 microRNA family is associated with developmental transitions in filarial nematode parasites
title_fullStr A novel member of the let-7 microRNA family is associated with developmental transitions in filarial nematode parasites
title_full_unstemmed A novel member of the let-7 microRNA family is associated with developmental transitions in filarial nematode parasites
title_short A novel member of the let-7 microRNA family is associated with developmental transitions in filarial nematode parasites
title_sort novel member of the let-7 microrna family is associated with developmental transitions in filarial nematode parasites
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4428239/
https://www.ncbi.nlm.nih.gov/pubmed/25896062
http://dx.doi.org/10.1186/s12864-015-1536-y
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