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Mapping the Pax6 3’ untranslated region microRNA regulatory landscape

BACKGROUND: PAX6 is a homeodomain transcription factor that acts in a highly dosage-sensitive manner to regulate the development and function of the eyes, nose, central nervous system, gut, and endocrine pancreas. Several individual microRNAs (miRNA) have been implicated in regulating PAX6 in differ...

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Autores principales: Ryan, Bridget C., Lowe, Kieran, Hanson, Laura, Gil, Talveen, Braun, Lauren, Howard, Perry L., Chow, Robert L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238409/
https://www.ncbi.nlm.nih.gov/pubmed/30442116
http://dx.doi.org/10.1186/s12864-018-5212-x
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author Ryan, Bridget C.
Lowe, Kieran
Hanson, Laura
Gil, Talveen
Braun, Lauren
Howard, Perry L.
Chow, Robert L.
author_facet Ryan, Bridget C.
Lowe, Kieran
Hanson, Laura
Gil, Talveen
Braun, Lauren
Howard, Perry L.
Chow, Robert L.
author_sort Ryan, Bridget C.
collection PubMed
description BACKGROUND: PAX6 is a homeodomain transcription factor that acts in a highly dosage-sensitive manner to regulate the development and function of the eyes, nose, central nervous system, gut, and endocrine pancreas. Several individual microRNAs (miRNA) have been implicated in regulating PAX6 in different cellular contexts, but a more general view of how they contribute to the fine-tuning and homeostasis of PAX6 is poorly understood. RESULTS: Here, a comprehensive analysis of the Pax6 3′ untranslated region was performed to map potential miRNA recognition elements and served as a backdrop for miRNA expression profiling experiments to identify potential cell/tissue-specific miRNA codes. Pax6 3’UTR pull-down studies identified a cohort of miRNA interactors in pancreatic αTC1–6 cells that, based on the spacing of their recognition sites in the Pax6 3’UTR, revealed 3 clusters where cooperative miRNA regulation may occur. Some of these interacting miRNAs have been implicated in α cell function but have not previously been linked to Pax6 function and may therefore represent novel PAX6 regulators. CONCLUSIONS: These findings reveal a regulatory landscape upon which miRNAs may participate in the developmental control, fine-tuning and/or homeostasis of PAX6 levels. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-018-5212-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-62384092018-11-26 Mapping the Pax6 3’ untranslated region microRNA regulatory landscape Ryan, Bridget C. Lowe, Kieran Hanson, Laura Gil, Talveen Braun, Lauren Howard, Perry L. Chow, Robert L. BMC Genomics Research Article BACKGROUND: PAX6 is a homeodomain transcription factor that acts in a highly dosage-sensitive manner to regulate the development and function of the eyes, nose, central nervous system, gut, and endocrine pancreas. Several individual microRNAs (miRNA) have been implicated in regulating PAX6 in different cellular contexts, but a more general view of how they contribute to the fine-tuning and homeostasis of PAX6 is poorly understood. RESULTS: Here, a comprehensive analysis of the Pax6 3′ untranslated region was performed to map potential miRNA recognition elements and served as a backdrop for miRNA expression profiling experiments to identify potential cell/tissue-specific miRNA codes. Pax6 3’UTR pull-down studies identified a cohort of miRNA interactors in pancreatic αTC1–6 cells that, based on the spacing of their recognition sites in the Pax6 3’UTR, revealed 3 clusters where cooperative miRNA regulation may occur. Some of these interacting miRNAs have been implicated in α cell function but have not previously been linked to Pax6 function and may therefore represent novel PAX6 regulators. CONCLUSIONS: These findings reveal a regulatory landscape upon which miRNAs may participate in the developmental control, fine-tuning and/or homeostasis of PAX6 levels. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12864-018-5212-x) contains supplementary material, which is available to authorized users. BioMed Central 2018-11-15 /pmc/articles/PMC6238409/ /pubmed/30442116 http://dx.doi.org/10.1186/s12864-018-5212-x Text en © The Author(s). 2018 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
Ryan, Bridget C.
Lowe, Kieran
Hanson, Laura
Gil, Talveen
Braun, Lauren
Howard, Perry L.
Chow, Robert L.
Mapping the Pax6 3’ untranslated region microRNA regulatory landscape
title Mapping the Pax6 3’ untranslated region microRNA regulatory landscape
title_full Mapping the Pax6 3’ untranslated region microRNA regulatory landscape
title_fullStr Mapping the Pax6 3’ untranslated region microRNA regulatory landscape
title_full_unstemmed Mapping the Pax6 3’ untranslated region microRNA regulatory landscape
title_short Mapping the Pax6 3’ untranslated region microRNA regulatory landscape
title_sort mapping the pax6 3’ untranslated region microrna regulatory landscape
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238409/
https://www.ncbi.nlm.nih.gov/pubmed/30442116
http://dx.doi.org/10.1186/s12864-018-5212-x
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