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, Professor 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 > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine |
| 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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