Profiling microRNAs through development of the parasitic nematode Haemonchus identifies nematode-specific miRNAs that suppress larval development

Marks, N. D. et al. (2019) Profiling microRNAs through development of the parasitic nematode Haemonchus identifies nematode-specific miRNAs that suppress larval development. Scientific Reports, 9, 17594. (doi: 10.1038/s41598-019-54154-6) (PMID:31772378) (PMCID:PMC6879476)

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Abstract

Parasitic nematodes transition between dramatically different free-living and parasitic stages, with correctly timed development and migration crucial to successful completion of their lifecycle. However little is known of the mechanisms controlling these transitions. microRNAs (miRNAs) negatively regulate gene expression post-transcriptionally and regulate development of diverse organisms. Here we used microarrays to determine the expression profile of miRNAs through development and in gut tissue of the pathogenic nematode Haemonchus contortus. Two miRNAs, mir-228 and mir-235, were enriched in infective L3 larvae, an arrested stage analogous to Caenorhabditis elegans dauer larvae. We hypothesized that these miRNAs may suppress development and maintain arrest. Consistent with this, inhibitors of these miRNAs promoted H. contortus development from L3 to L4 stage, while genetic deletion of C. elegans homologous miRNAs reduced dauer arrest. Epistasis studies with C. elegans daf-2 mutants showed that mir-228 and mir-235 synergise with FOXO transcription factor DAF-16 in the insulin signaling pathway. Target prediction suggests that these miRNAs suppress metabolic and transcription factor activity required for development. Our results provide novel insight into the expression and functions of specific miRNAs in regulating nematode development and identify miRNAs and their target genes as potential therapeutic targets to limit parasite survival within the host.

Item Type:Articles
Additional Information:This work was supported by the UK Biotechnology and Biological Sciences Research Council (BBSRC)/Knowledge Transfer Network/Zoetis (CASE studentship BB/J500732/1) (NDM), BBSRC (BB/M003949) (K.M., R.L., C.B., E.D.), The Wellcome Trust (WT 086823/Z/08/Z; ADW) (WT 098051; AM), (WT 094751; V.G.), Agriculture and Horticulture Development Board and University of Glasgow (Industrial Partnership PhD) (HYG), European Commission FP7 PARAVAC consortium (B.R.), University of Glasgow and Moredun Scientific (Industrial Partnership PhD) (EH) and MMVP UK (No. CZ.02.2.69/0.0/0.0/16_027/0008495) (MA).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Devaney, Professor Eileen and Hanks, Eve and Roberts, Dr Brett and Maitland, Ms Kirsty and Winter, Dr Alan and Laing, Dr Roz and Towne, Miss Jessica and Britton, Dr Collette and Gillan, Dr Victoria and Ambroz, Mr Martin
Authors: Marks, N. D., Winter, A. D., Gu, H. Y., Maitland, K., Gillan, V., Ambroz, M., Martinelli, A., Laing, R., MacLellan, R., Towne, J., Roberts, B., Hanks, E., Devaney, E., and Britton, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Scientific Reports
Publisher:Nature Research
ISSN:2045-2322
ISSN (Online):2045-2322
Published Online:26 November 2019
Copyright Holders:Copyright © The Authors 2019
First Published:First published in Scientific Reports 9:17594
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190824The BUG consortium Building Upon the Genome: using H. contortus genomic resources to develop novel interventions to control endemic GI parasitesEileen DevaneyBiotechnology and Biological Sciences Research Council (BBSRC)BB/M003949/1Institute of Biodiversity, Animal Health and Comparative Medicine
165640Genetic control of parasitic nematode development by microRNAsCollette BrittonBiotechnology and Biological Sciences Research Council (BBSRC)BB/J500732/1Institute of Biodiversity, Animal Health and Comparative Medicine
165089microRNAs and drug resistance in parasitic nematodesEileen DevaneyWellcome Trust (WELLCOTR)094751/Z/10/ZInstitute of Biodiversity, Animal Health and Comparative Medicine