miR-190 Enhances HIF-Dependent Responses to Hypoxia in Drosophila by Inhibiting the Prolyl-4-hydroxylase Fatiga

Cellular and systemic responses to low oxygen levels are principally mediated by Hypoxia Inducible Factors (HIFs), a family of evolutionary conserved heterodimeric transcription factors, whose alpha- and beta-subunits belong to the bHLH-PAS family. In normoxia, HIFα is hydroxylated by specific proly...

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Autores principales:	Melani, Mariana, Wappner, Pablo
Publicado:	2016
Materias:	Fatiga hypoxia inducible factor hypoxia inducible factor 1alpha hypoxia inducible factor 1beta hypoxia inducible factor proline dioxygenase microRNA microRNA 190 Sima transcription factor GAL4 unclassified drug oxygen procollagen proline 2 oxoglutarate 4 dioxygenase 3' untranslated region Article controlled study Drosophila melanogaster embryo environmental stress enzyme inhibition gene interaction gene overexpression hypoxia lethality loss of function mutation nonhuman oxygen supply phenotype protein degradation protein expression protein function protein stability pupa RNA interference trachea animal biosynthesis cell hypoxia gene expression regulation genetic transcription genetics growth, development and aging human metabolism Animals Cell Hypoxia Gene Expression Regulation Humans Hypoxia-Inducible Factor 1, alpha Subunit MicroRNAs Oxygen Prolyl Hydroxylases Transcription, Genetic
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15537390_v12_n5_p_DeLellaEzcurra http://hdl.handle.net/20.500.12110/paper_15537390_v12_n5_p_DeLellaEzcurra
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_15537390_v12_n5_p_DeLellaEzcurra
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spelling	paper:paper_15537390_v12_n5_p_DeLellaEzcurra2023-06-08T16:23:11Z miR-190 Enhances HIF-Dependent Responses to Hypoxia in Drosophila by Inhibiting the Prolyl-4-hydroxylase Fatiga Melani, Mariana Wappner, Pablo Fatiga hypoxia inducible factor hypoxia inducible factor 1alpha hypoxia inducible factor 1beta hypoxia inducible factor proline dioxygenase microRNA microRNA 190 Sima transcription factor GAL4 unclassified drug hypoxia inducible factor 1alpha microRNA oxygen procollagen proline 2 oxoglutarate 4 dioxygenase 3' untranslated region Article controlled study Drosophila melanogaster embryo environmental stress enzyme inhibition gene interaction gene overexpression hypoxia lethality loss of function mutation nonhuman oxygen supply phenotype protein degradation protein expression protein function protein stability pupa RNA interference trachea animal biosynthesis cell hypoxia gene expression regulation genetic transcription genetics growth, development and aging human metabolism Animals Cell Hypoxia Drosophila melanogaster Gene Expression Regulation Humans Hypoxia-Inducible Factor 1, alpha Subunit MicroRNAs Oxygen Prolyl Hydroxylases Transcription, Genetic Cellular and systemic responses to low oxygen levels are principally mediated by Hypoxia Inducible Factors (HIFs), a family of evolutionary conserved heterodimeric transcription factors, whose alpha- and beta-subunits belong to the bHLH-PAS family. In normoxia, HIFα is hydroxylated by specific prolyl-4-hydroxylases, targeting it for proteasomal degradation, while in hypoxia the activity of these hydroxylases decreases due to low oxygen availability, leading to HIFα accumulation and expression of HIF target genes. To identify microRNAs required for maximal HIF activity, we conducted an overexpression screen in Drosophila melanogaster, evaluating the induction of a HIF transcriptional reporter. miR-190 overexpression enhanced HIF-dependent biological responses, including terminal sprouting of the tracheal system, while in miR-190 loss of function embryos the hypoxic response was impaired. In hypoxic conditions, miR-190 expression was upregulated and required for induction of HIF target genes by directly inhibiting the HIF prolyl-4-hydroxylase Fatiga. Thus, miR-190 is a novel regulator of the hypoxia response that represses the oxygen sensor Fatiga, leading to HIFα stabilization and enhancement of hypoxic responses. © 2016 De Lella Ezcurra et al. Fil:Melani, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Wappner, P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2016 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15537390_v12_n5_p_DeLellaEzcurra http://hdl.handle.net/20.500.12110/paper_15537390_v12_n5_p_DeLellaEzcurra
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Fatiga hypoxia inducible factor hypoxia inducible factor 1alpha hypoxia inducible factor 1beta hypoxia inducible factor proline dioxygenase microRNA microRNA 190 Sima transcription factor GAL4 unclassified drug hypoxia inducible factor 1alpha microRNA oxygen procollagen proline 2 oxoglutarate 4 dioxygenase 3' untranslated region Article controlled study Drosophila melanogaster embryo environmental stress enzyme inhibition gene interaction gene overexpression hypoxia lethality loss of function mutation nonhuman oxygen supply phenotype protein degradation protein expression protein function protein stability pupa RNA interference trachea animal biosynthesis cell hypoxia gene expression regulation genetic transcription genetics growth, development and aging human metabolism Animals Cell Hypoxia Drosophila melanogaster Gene Expression Regulation Humans Hypoxia-Inducible Factor 1, alpha Subunit MicroRNAs Oxygen Prolyl Hydroxylases Transcription, Genetic
spellingShingle	Fatiga hypoxia inducible factor hypoxia inducible factor 1alpha hypoxia inducible factor 1beta hypoxia inducible factor proline dioxygenase microRNA microRNA 190 Sima transcription factor GAL4 unclassified drug hypoxia inducible factor 1alpha microRNA oxygen procollagen proline 2 oxoglutarate 4 dioxygenase 3' untranslated region Article controlled study Drosophila melanogaster embryo environmental stress enzyme inhibition gene interaction gene overexpression hypoxia lethality loss of function mutation nonhuman oxygen supply phenotype protein degradation protein expression protein function protein stability pupa RNA interference trachea animal biosynthesis cell hypoxia gene expression regulation genetic transcription genetics growth, development and aging human metabolism Animals Cell Hypoxia Drosophila melanogaster Gene Expression Regulation Humans Hypoxia-Inducible Factor 1, alpha Subunit MicroRNAs Oxygen Prolyl Hydroxylases Transcription, Genetic Melani, Mariana Wappner, Pablo miR-190 Enhances HIF-Dependent Responses to Hypoxia in Drosophila by Inhibiting the Prolyl-4-hydroxylase Fatiga
topic_facet	Fatiga hypoxia inducible factor hypoxia inducible factor 1alpha hypoxia inducible factor 1beta hypoxia inducible factor proline dioxygenase microRNA microRNA 190 Sima transcription factor GAL4 unclassified drug hypoxia inducible factor 1alpha microRNA oxygen procollagen proline 2 oxoglutarate 4 dioxygenase 3' untranslated region Article controlled study Drosophila melanogaster embryo environmental stress enzyme inhibition gene interaction gene overexpression hypoxia lethality loss of function mutation nonhuman oxygen supply phenotype protein degradation protein expression protein function protein stability pupa RNA interference trachea animal biosynthesis cell hypoxia gene expression regulation genetic transcription genetics growth, development and aging human metabolism Animals Cell Hypoxia Drosophila melanogaster Gene Expression Regulation Humans Hypoxia-Inducible Factor 1, alpha Subunit MicroRNAs Oxygen Prolyl Hydroxylases Transcription, Genetic
description	Cellular and systemic responses to low oxygen levels are principally mediated by Hypoxia Inducible Factors (HIFs), a family of evolutionary conserved heterodimeric transcription factors, whose alpha- and beta-subunits belong to the bHLH-PAS family. In normoxia, HIFα is hydroxylated by specific prolyl-4-hydroxylases, targeting it for proteasomal degradation, while in hypoxia the activity of these hydroxylases decreases due to low oxygen availability, leading to HIFα accumulation and expression of HIF target genes. To identify microRNAs required for maximal HIF activity, we conducted an overexpression screen in Drosophila melanogaster, evaluating the induction of a HIF transcriptional reporter. miR-190 overexpression enhanced HIF-dependent biological responses, including terminal sprouting of the tracheal system, while in miR-190 loss of function embryos the hypoxic response was impaired. In hypoxic conditions, miR-190 expression was upregulated and required for induction of HIF target genes by directly inhibiting the HIF prolyl-4-hydroxylase Fatiga. Thus, miR-190 is a novel regulator of the hypoxia response that represses the oxygen sensor Fatiga, leading to HIFα stabilization and enhancement of hypoxic responses. © 2016 De Lella Ezcurra et al.
author	Melani, Mariana Wappner, Pablo
author_facet	Melani, Mariana Wappner, Pablo
author_sort	Melani, Mariana
title	miR-190 Enhances HIF-Dependent Responses to Hypoxia in Drosophila by Inhibiting the Prolyl-4-hydroxylase Fatiga
title_short	miR-190 Enhances HIF-Dependent Responses to Hypoxia in Drosophila by Inhibiting the Prolyl-4-hydroxylase Fatiga
title_full	miR-190 Enhances HIF-Dependent Responses to Hypoxia in Drosophila by Inhibiting the Prolyl-4-hydroxylase Fatiga
title_fullStr	miR-190 Enhances HIF-Dependent Responses to Hypoxia in Drosophila by Inhibiting the Prolyl-4-hydroxylase Fatiga
title_full_unstemmed	miR-190 Enhances HIF-Dependent Responses to Hypoxia in Drosophila by Inhibiting the Prolyl-4-hydroxylase Fatiga
title_sort	mir-190 enhances hif-dependent responses to hypoxia in drosophila by inhibiting the prolyl-4-hydroxylase fatiga
publishDate	2016
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15537390_v12_n5_p_DeLellaEzcurra http://hdl.handle.net/20.500.12110/paper_15537390_v12_n5_p_DeLellaEzcurra
work_keys_str_mv	AT melanimariana mir190enhanceshifdependentresponsestohypoxiaindrosophilabyinhibitingtheprolyl4hydroxylasefatiga AT wappnerpablo mir190enhanceshifdependentresponsestohypoxiaindrosophilabyinhibitingtheprolyl4hydroxylasefatiga
_version_	1768543390580867072

miR-190 Enhances HIF-Dependent Responses to Hypoxia in Drosophila by Inhibiting the Prolyl-4-hydroxylase Fatiga

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