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Aedes aegypti miRNA-33 modulates permethrin induced toxicity by regulating VGSC transcripts

Aedes aegypti is a major vector of Zika, dengue, and other arboviruses. Permethrin adulticidal spraying, which targets the voltage-gated sodium channel (VGSC), is commonly done to reduce local mosquito populations and protect humans from exposure to arbovirus pathogens transmitted by this dangerous...

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Autores principales: Kubik, Tristan D., Snell, Trey K., Saavedra-Rodriguez, Karla, Wilusz, Jeffrey, Anderson, John R., Lozano-Fuentes, Saul, Black, William C., Campbell, Corey L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012613/
https://www.ncbi.nlm.nih.gov/pubmed/33790374
http://dx.doi.org/10.1038/s41598-021-86665-6
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author Kubik, Tristan D.
Snell, Trey K.
Saavedra-Rodriguez, Karla
Wilusz, Jeffrey
Anderson, John R.
Lozano-Fuentes, Saul
Black, William C.
Campbell, Corey L.
author_facet Kubik, Tristan D.
Snell, Trey K.
Saavedra-Rodriguez, Karla
Wilusz, Jeffrey
Anderson, John R.
Lozano-Fuentes, Saul
Black, William C.
Campbell, Corey L.
author_sort Kubik, Tristan D.
collection PubMed
description Aedes aegypti is a major vector of Zika, dengue, and other arboviruses. Permethrin adulticidal spraying, which targets the voltage-gated sodium channel (VGSC), is commonly done to reduce local mosquito populations and protect humans from exposure to arbovirus pathogens transmitted by this dangerous pest. Permethrin resistance, however, is a growing problem and understanding its underlying molecular basis may identify avenues to combat it. We identified a single G:C polymorphism in pre-miR-33 that was genetically associated with permethrin resistance; resulting isoforms had structural differences that may affect DICER-1/pre-miRNA processing rates. We then assessed the effects of overexpression of pre-miR-33 isoforms on permethrin toxicological phenotypes, VGSC transcript abundance and protein levels for two genetically related mosquito strains. One strain had its naturally high permethrin resistance levels maintained by periodic treatment, and the other was released from selection. VGSC protein levels were lower in the permethrin resistant strain than in the related permethrin-susceptible strain. Overexpression of the G-pre-miR-33 isoform reduced VGSC expression levels in both strains. To further elucidate changes in gene expression associated with permethrin resistance, exome-capture gDNA deep sequencing, genetic association mapping and subsequent gene set enrichment analysis revealed that transport genes, in particular, were selected in resistant versus susceptible mosquitoes. Collectively, these data indicate that miR-33 regulates VGSC expression as part of a nuanced system of neuronal regulation that contributes to a network of heritable features determining permethrin resistance.
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spelling pubmed-80126132021-04-05 Aedes aegypti miRNA-33 modulates permethrin induced toxicity by regulating VGSC transcripts Kubik, Tristan D. Snell, Trey K. Saavedra-Rodriguez, Karla Wilusz, Jeffrey Anderson, John R. Lozano-Fuentes, Saul Black, William C. Campbell, Corey L. Sci Rep Article Aedes aegypti is a major vector of Zika, dengue, and other arboviruses. Permethrin adulticidal spraying, which targets the voltage-gated sodium channel (VGSC), is commonly done to reduce local mosquito populations and protect humans from exposure to arbovirus pathogens transmitted by this dangerous pest. Permethrin resistance, however, is a growing problem and understanding its underlying molecular basis may identify avenues to combat it. We identified a single G:C polymorphism in pre-miR-33 that was genetically associated with permethrin resistance; resulting isoforms had structural differences that may affect DICER-1/pre-miRNA processing rates. We then assessed the effects of overexpression of pre-miR-33 isoforms on permethrin toxicological phenotypes, VGSC transcript abundance and protein levels for two genetically related mosquito strains. One strain had its naturally high permethrin resistance levels maintained by periodic treatment, and the other was released from selection. VGSC protein levels were lower in the permethrin resistant strain than in the related permethrin-susceptible strain. Overexpression of the G-pre-miR-33 isoform reduced VGSC expression levels in both strains. To further elucidate changes in gene expression associated with permethrin resistance, exome-capture gDNA deep sequencing, genetic association mapping and subsequent gene set enrichment analysis revealed that transport genes, in particular, were selected in resistant versus susceptible mosquitoes. Collectively, these data indicate that miR-33 regulates VGSC expression as part of a nuanced system of neuronal regulation that contributes to a network of heritable features determining permethrin resistance. Nature Publishing Group UK 2021-03-31 /pmc/articles/PMC8012613/ /pubmed/33790374 http://dx.doi.org/10.1038/s41598-021-86665-6 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kubik, Tristan D.
Snell, Trey K.
Saavedra-Rodriguez, Karla
Wilusz, Jeffrey
Anderson, John R.
Lozano-Fuentes, Saul
Black, William C.
Campbell, Corey L.
Aedes aegypti miRNA-33 modulates permethrin induced toxicity by regulating VGSC transcripts
title Aedes aegypti miRNA-33 modulates permethrin induced toxicity by regulating VGSC transcripts
title_full Aedes aegypti miRNA-33 modulates permethrin induced toxicity by regulating VGSC transcripts
title_fullStr Aedes aegypti miRNA-33 modulates permethrin induced toxicity by regulating VGSC transcripts
title_full_unstemmed Aedes aegypti miRNA-33 modulates permethrin induced toxicity by regulating VGSC transcripts
title_short Aedes aegypti miRNA-33 modulates permethrin induced toxicity by regulating VGSC transcripts
title_sort aedes aegypti mirna-33 modulates permethrin induced toxicity by regulating vgsc transcripts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012613/
https://www.ncbi.nlm.nih.gov/pubmed/33790374
http://dx.doi.org/10.1038/s41598-021-86665-6
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