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Computational characterization of Iron metabolism in the Tsetse disease vector, Glossina morsitans: IRE stem-loops
BACKGROUND: Iron metabolism and regulation is an indispensable part of species survival, most importantly for blood feeding insects. Iron regulatory proteins are central regulators of iron homeostasis, whose binding to iron response element (IRE) stem-loop structures within the UTRs of genes regulat...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4977773/ https://www.ncbi.nlm.nih.gov/pubmed/27503259 http://dx.doi.org/10.1186/s12864-016-2932-7 |
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author | Dashti, Zahra Jalali Sefid Gamieldien, Junaid Christoffels, Alan |
author_facet | Dashti, Zahra Jalali Sefid Gamieldien, Junaid Christoffels, Alan |
author_sort | Dashti, Zahra Jalali Sefid |
collection | PubMed |
description | BACKGROUND: Iron metabolism and regulation is an indispensable part of species survival, most importantly for blood feeding insects. Iron regulatory proteins are central regulators of iron homeostasis, whose binding to iron response element (IRE) stem-loop structures within the UTRs of genes regulate expression at the post-transcriptional level. Despite the extensive literature on the mechanism of iron regulation in human, less attention has been given to insect and more specifically the blood feeding insects, where research has mainly focused on the characterization of ferritin and transferrin. We thus, examined the mechanism of iron homeostasis through a genome-wide computational identification of IREs and other enriched motifs in the UTRs of Glossina morsitans with the view to identify new IRE-regulated genes. RESULTS: We identified 150 genes, of which two are known to contain IREs, namely the ferritin heavy chain and the MRCK-alpha. The remainder of the identified genes is considered novel including 20 hypothetical proteins, for which an iron-regulatory mechanism of action was inferred. Forty-three genes were found with IRE-signatures of regulation in two or more insects, while 46 were only found to be IRE-regulated in two species. Notably 39 % of the identified genes exclusively shared IRE-signatures in other Glossina species, which are potentially Glossina-specific adaptive measures in addressing its unique reproductive biology and blood meal-induced iron overload. In line with previous findings, we found no evidence pertaining to an IRE regulation of Transferrin, which highlight the importance of ferritin heavy chain and the other proposed transporters in the tsetse fly. In the context of iron-sequestration, key players of tsetse immune defence against trypanosomes have been introduced namely 14 stress and immune response genes, while 28 cell-envelop, transport, and binding genes were assigned a putative role in iron trafficking. Additionally, we identified and annotated enriched motifs in the UTRs of the putative IRE-regulated genes to derive at a co-regulatory network that maintains iron homeostasis in tsetse flies. Three putative microRNA-binding sites namely Gy-box, Brd-box and K-box motifs were identified among the regulatory motifs, enriched in the UTRs of the putative IRE-regulated genes. CONCLUSION: Beyond our current view of iron metabolism in insects, with ferritin and transferrin as its key players, this study provides a comprehensive catalogue of genes with possible roles in the acquisition; transport and storage of iron hence iron homeostasis in the tsetse fly. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2932-7) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4977773 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-49777732016-08-10 Computational characterization of Iron metabolism in the Tsetse disease vector, Glossina morsitans: IRE stem-loops Dashti, Zahra Jalali Sefid Gamieldien, Junaid Christoffels, Alan BMC Genomics Research Article BACKGROUND: Iron metabolism and regulation is an indispensable part of species survival, most importantly for blood feeding insects. Iron regulatory proteins are central regulators of iron homeostasis, whose binding to iron response element (IRE) stem-loop structures within the UTRs of genes regulate expression at the post-transcriptional level. Despite the extensive literature on the mechanism of iron regulation in human, less attention has been given to insect and more specifically the blood feeding insects, where research has mainly focused on the characterization of ferritin and transferrin. We thus, examined the mechanism of iron homeostasis through a genome-wide computational identification of IREs and other enriched motifs in the UTRs of Glossina morsitans with the view to identify new IRE-regulated genes. RESULTS: We identified 150 genes, of which two are known to contain IREs, namely the ferritin heavy chain and the MRCK-alpha. The remainder of the identified genes is considered novel including 20 hypothetical proteins, for which an iron-regulatory mechanism of action was inferred. Forty-three genes were found with IRE-signatures of regulation in two or more insects, while 46 were only found to be IRE-regulated in two species. Notably 39 % of the identified genes exclusively shared IRE-signatures in other Glossina species, which are potentially Glossina-specific adaptive measures in addressing its unique reproductive biology and blood meal-induced iron overload. In line with previous findings, we found no evidence pertaining to an IRE regulation of Transferrin, which highlight the importance of ferritin heavy chain and the other proposed transporters in the tsetse fly. In the context of iron-sequestration, key players of tsetse immune defence against trypanosomes have been introduced namely 14 stress and immune response genes, while 28 cell-envelop, transport, and binding genes were assigned a putative role in iron trafficking. Additionally, we identified and annotated enriched motifs in the UTRs of the putative IRE-regulated genes to derive at a co-regulatory network that maintains iron homeostasis in tsetse flies. Three putative microRNA-binding sites namely Gy-box, Brd-box and K-box motifs were identified among the regulatory motifs, enriched in the UTRs of the putative IRE-regulated genes. CONCLUSION: Beyond our current view of iron metabolism in insects, with ferritin and transferrin as its key players, this study provides a comprehensive catalogue of genes with possible roles in the acquisition; transport and storage of iron hence iron homeostasis in the tsetse fly. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2932-7) contains supplementary material, which is available to authorized users. BioMed Central 2016-08-08 /pmc/articles/PMC4977773/ /pubmed/27503259 http://dx.doi.org/10.1186/s12864-016-2932-7 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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 Dashti, Zahra Jalali Sefid Gamieldien, Junaid Christoffels, Alan Computational characterization of Iron metabolism in the Tsetse disease vector, Glossina morsitans: IRE stem-loops |
title | Computational characterization of Iron metabolism in the Tsetse disease vector, Glossina morsitans: IRE stem-loops |
title_full | Computational characterization of Iron metabolism in the Tsetse disease vector, Glossina morsitans: IRE stem-loops |
title_fullStr | Computational characterization of Iron metabolism in the Tsetse disease vector, Glossina morsitans: IRE stem-loops |
title_full_unstemmed | Computational characterization of Iron metabolism in the Tsetse disease vector, Glossina morsitans: IRE stem-loops |
title_short | Computational characterization of Iron metabolism in the Tsetse disease vector, Glossina morsitans: IRE stem-loops |
title_sort | computational characterization of iron metabolism in the tsetse disease vector, glossina morsitans: ire stem-loops |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4977773/ https://www.ncbi.nlm.nih.gov/pubmed/27503259 http://dx.doi.org/10.1186/s12864-016-2932-7 |
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