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MicroRNA-275 targets sarco/endoplasmic reticulum Ca(2+) adenosine triphosphatase (SERCA) to control key functions in the mosquito gut

The yellow fever mosquito Aedes aegypti is the major vector of arboviruses, causing numerous devastating human diseases, such as dengue and yellow fevers, Chikungunya and Zika. Female mosquitoes need vertebrate blood for egg development, and repeated cycles of blood feeding are tightly linked to pat...

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Autores principales: Zhao, Bo, Lucas, Keira J., Saha, Tusar T., Ha, Jisu, Ling, Lin, Kokoza, Vladimir A., Roy, Sourav, Raikhel, Alexander S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560755/
https://www.ncbi.nlm.nih.gov/pubmed/28787446
http://dx.doi.org/10.1371/journal.pgen.1006943
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author Zhao, Bo
Lucas, Keira J.
Saha, Tusar T.
Ha, Jisu
Ling, Lin
Kokoza, Vladimir A.
Roy, Sourav
Raikhel, Alexander S.
author_facet Zhao, Bo
Lucas, Keira J.
Saha, Tusar T.
Ha, Jisu
Ling, Lin
Kokoza, Vladimir A.
Roy, Sourav
Raikhel, Alexander S.
author_sort Zhao, Bo
collection PubMed
description The yellow fever mosquito Aedes aegypti is the major vector of arboviruses, causing numerous devastating human diseases, such as dengue and yellow fevers, Chikungunya and Zika. Female mosquitoes need vertebrate blood for egg development, and repeated cycles of blood feeding are tightly linked to pathogen transmission. The mosquito’s posterior midgut (gut) is involved in blood digestion and also serves as an entry point for pathogens. Thus, the mosquito gut is an important tissue to investigate. The miRNA aae-miR-275 (miR-275) has been shown to be required for normal blood digestion in the female mosquito; however, the mechanism of its action has remained unknown. Here, we demonstrate that miR-275 directly targets and positively regulates sarco/endoplasmic reticulum Ca(2+) adenosine triphosphatase, which is implicated in active transport of Ca(2+) from the cytosol to the sarco/endoplasmic reticulum. We utilized a combination of the gut-specific yeast transcription activator protein Gal4/upstream activating sequence (Gal4/UAS) system and miRNA Tough Decoy technology to deplete the endogenous level of miR-275 in guts of transgenic mosquitoes. This gut-specific reduction of miR-275 post blood meal decreased SERCA mRNA and protein levels of the digestive enzyme late trypsin. It also resulted in a significant reduction of gut microbiota. Moreover, the decrease of miR-275 and SERCA correlated with defects in the Notch signaling pathway and assembly of the gut actin cytoskeleton. The adverse phenotypes caused by miR-275 silencing were rescued by injections of miR-275 mimic. Thus, we have discovered that miR-275 directly targets SERCA, and the maintenance of its level is critical for multiple gut functions in mosquitoes.
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spelling pubmed-55607552017-08-25 MicroRNA-275 targets sarco/endoplasmic reticulum Ca(2+) adenosine triphosphatase (SERCA) to control key functions in the mosquito gut Zhao, Bo Lucas, Keira J. Saha, Tusar T. Ha, Jisu Ling, Lin Kokoza, Vladimir A. Roy, Sourav Raikhel, Alexander S. PLoS Genet Research Article The yellow fever mosquito Aedes aegypti is the major vector of arboviruses, causing numerous devastating human diseases, such as dengue and yellow fevers, Chikungunya and Zika. Female mosquitoes need vertebrate blood for egg development, and repeated cycles of blood feeding are tightly linked to pathogen transmission. The mosquito’s posterior midgut (gut) is involved in blood digestion and also serves as an entry point for pathogens. Thus, the mosquito gut is an important tissue to investigate. The miRNA aae-miR-275 (miR-275) has been shown to be required for normal blood digestion in the female mosquito; however, the mechanism of its action has remained unknown. Here, we demonstrate that miR-275 directly targets and positively regulates sarco/endoplasmic reticulum Ca(2+) adenosine triphosphatase, which is implicated in active transport of Ca(2+) from the cytosol to the sarco/endoplasmic reticulum. We utilized a combination of the gut-specific yeast transcription activator protein Gal4/upstream activating sequence (Gal4/UAS) system and miRNA Tough Decoy technology to deplete the endogenous level of miR-275 in guts of transgenic mosquitoes. This gut-specific reduction of miR-275 post blood meal decreased SERCA mRNA and protein levels of the digestive enzyme late trypsin. It also resulted in a significant reduction of gut microbiota. Moreover, the decrease of miR-275 and SERCA correlated with defects in the Notch signaling pathway and assembly of the gut actin cytoskeleton. The adverse phenotypes caused by miR-275 silencing were rescued by injections of miR-275 mimic. Thus, we have discovered that miR-275 directly targets SERCA, and the maintenance of its level is critical for multiple gut functions in mosquitoes. Public Library of Science 2017-08-07 /pmc/articles/PMC5560755/ /pubmed/28787446 http://dx.doi.org/10.1371/journal.pgen.1006943 Text en © 2017 Zhao et al http://creativecommons.org/licenses/by/4.0/ 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 author and source are credited.
spellingShingle Research Article
Zhao, Bo
Lucas, Keira J.
Saha, Tusar T.
Ha, Jisu
Ling, Lin
Kokoza, Vladimir A.
Roy, Sourav
Raikhel, Alexander S.
MicroRNA-275 targets sarco/endoplasmic reticulum Ca(2+) adenosine triphosphatase (SERCA) to control key functions in the mosquito gut
title MicroRNA-275 targets sarco/endoplasmic reticulum Ca(2+) adenosine triphosphatase (SERCA) to control key functions in the mosquito gut
title_full MicroRNA-275 targets sarco/endoplasmic reticulum Ca(2+) adenosine triphosphatase (SERCA) to control key functions in the mosquito gut
title_fullStr MicroRNA-275 targets sarco/endoplasmic reticulum Ca(2+) adenosine triphosphatase (SERCA) to control key functions in the mosquito gut
title_full_unstemmed MicroRNA-275 targets sarco/endoplasmic reticulum Ca(2+) adenosine triphosphatase (SERCA) to control key functions in the mosquito gut
title_short MicroRNA-275 targets sarco/endoplasmic reticulum Ca(2+) adenosine triphosphatase (SERCA) to control key functions in the mosquito gut
title_sort microrna-275 targets sarco/endoplasmic reticulum ca(2+) adenosine triphosphatase (serca) to control key functions in the mosquito gut
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560755/
https://www.ncbi.nlm.nih.gov/pubmed/28787446
http://dx.doi.org/10.1371/journal.pgen.1006943
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