Musashi mediates translational repression of the Drosophila hypoxia inducible factor

Adaptation to hypoxia depends on a conserved α/β heterodimeric transcription factor called Hypoxia Inducible Factor (HIF), whose α-subunit is regulated by oxygen through different concurrent mechanisms. In this study, we have identified the RNA binding protein dMusashi, as a negative regulator of th...

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Autores principales:	Bertolin, A.P., Katz, M.J., Yano, M., Pozzi, B., Acevedo, J.M., Blanco-Obregón, D., Gándara, L., Sorianello, E., Kanda, H., Okano, H., Srebrow, A., Wappner, P.
Formato:	JOUR
Materias:	hypoxia inducible factor Musashi protein Musashi1 protein RNA binding protein unclassified drug DNA binding protein Drosophila protein hypoxia inducible factor 1alpha messenger RNA musashi protein, Drosophila protein binding Sima protein, Drosophila 3' untranslated region animal cell animal tissue Article cell hypoxia controlled study down regulation Drosophila melanogaster embryo gene expression gene interaction insect cell culture mouse nonhuman priority journal protein protein interaction translation regulation animal biological model embryology gene locus genetic transcription genetics growth, development and aging mammal metabolism nucleotide sequence protein synthesis signal transduction trachea Animals Base Sequence DNA-Binding Proteins Down-Regulation Drosophila Proteins Genetic Loci Hypoxia-Inducible Factor 1, alpha Subunit Mammals Models, Biological Protein Binding Protein Biosynthesis RNA, Messenger RNA-Binding Proteins Signal Transduction Trachea Transcription, Genetic
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_03051048_v44_n16_p7555_Bertolin
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	todo:paper_03051048_v44_n16_p7555_Bertolin
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spelling	todo:paper_03051048_v44_n16_p7555_Bertolin2023-10-03T15:21:33Z Musashi mediates translational repression of the Drosophila hypoxia inducible factor Bertolin, A.P. Katz, M.J. Yano, M. Pozzi, B. Acevedo, J.M. Blanco-Obregón, D. Gándara, L. Sorianello, E. Kanda, H. Okano, H. Srebrow, A. Wappner, P. hypoxia inducible factor Musashi protein Musashi1 protein RNA binding protein unclassified drug DNA binding protein Drosophila protein hypoxia inducible factor 1alpha messenger RNA musashi protein, Drosophila protein binding RNA binding protein Sima protein, Drosophila 3' untranslated region animal cell animal tissue Article cell hypoxia controlled study down regulation Drosophila melanogaster embryo gene expression gene interaction insect cell culture mouse nonhuman priority journal protein protein interaction translation regulation animal biological model embryology gene locus genetic transcription genetics growth, development and aging mammal metabolism nucleotide sequence protein synthesis signal transduction trachea Animals Base Sequence DNA-Binding Proteins Down-Regulation Drosophila melanogaster Drosophila Proteins Genetic Loci Hypoxia-Inducible Factor 1, alpha Subunit Mammals Models, Biological Protein Binding Protein Biosynthesis RNA, Messenger RNA-Binding Proteins Signal Transduction Trachea Transcription, Genetic Adaptation to hypoxia depends on a conserved α/β heterodimeric transcription factor called Hypoxia Inducible Factor (HIF), whose α-subunit is regulated by oxygen through different concurrent mechanisms. In this study, we have identified the RNA binding protein dMusashi, as a negative regulator of the fly HIF homologue Sima. Genetic interaction assays suggested that dMusashi participates of the HIF pathway, and molecular studies carried out in Drosophila cell cultures showed that dMusashi recognizes a Musashi Binding Element in the 3′ UTR of the HIFα transcript, thereby mediating its translational repression in normoxia. In hypoxic conditions dMusashi is downregulated, lifting HIFα repression and contributing to trigger HIF-dependent gene expression. Analysis performed in mouse brains revealed that murine Msi1 protein physically interacts with HIF-1α transcript, suggesting that the regulation of HIF by Msi might be conserved in mammalian systems. Thus, Musashi is a novel regulator of HIF that inhibits responses to hypoxia specifically when oxygen is available. © 2016 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research. Fil:Pozzi, B. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Acevedo, J.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Sorianello, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Srebrow, A. 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_03051048_v44_n16_p7555_Bertolin
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	hypoxia inducible factor Musashi protein Musashi1 protein RNA binding protein unclassified drug DNA binding protein Drosophila protein hypoxia inducible factor 1alpha messenger RNA musashi protein, Drosophila protein binding RNA binding protein Sima protein, Drosophila 3' untranslated region animal cell animal tissue Article cell hypoxia controlled study down regulation Drosophila melanogaster embryo gene expression gene interaction insect cell culture mouse nonhuman priority journal protein protein interaction translation regulation animal biological model embryology gene locus genetic transcription genetics growth, development and aging mammal metabolism nucleotide sequence protein synthesis signal transduction trachea Animals Base Sequence DNA-Binding Proteins Down-Regulation Drosophila melanogaster Drosophila Proteins Genetic Loci Hypoxia-Inducible Factor 1, alpha Subunit Mammals Models, Biological Protein Binding Protein Biosynthesis RNA, Messenger RNA-Binding Proteins Signal Transduction Trachea Transcription, Genetic
spellingShingle	hypoxia inducible factor Musashi protein Musashi1 protein RNA binding protein unclassified drug DNA binding protein Drosophila protein hypoxia inducible factor 1alpha messenger RNA musashi protein, Drosophila protein binding RNA binding protein Sima protein, Drosophila 3' untranslated region animal cell animal tissue Article cell hypoxia controlled study down regulation Drosophila melanogaster embryo gene expression gene interaction insect cell culture mouse nonhuman priority journal protein protein interaction translation regulation animal biological model embryology gene locus genetic transcription genetics growth, development and aging mammal metabolism nucleotide sequence protein synthesis signal transduction trachea Animals Base Sequence DNA-Binding Proteins Down-Regulation Drosophila melanogaster Drosophila Proteins Genetic Loci Hypoxia-Inducible Factor 1, alpha Subunit Mammals Models, Biological Protein Binding Protein Biosynthesis RNA, Messenger RNA-Binding Proteins Signal Transduction Trachea Transcription, Genetic Bertolin, A.P. Katz, M.J. Yano, M. Pozzi, B. Acevedo, J.M. Blanco-Obregón, D. Gándara, L. Sorianello, E. Kanda, H. Okano, H. Srebrow, A. Wappner, P. Musashi mediates translational repression of the Drosophila hypoxia inducible factor
topic_facet	hypoxia inducible factor Musashi protein Musashi1 protein RNA binding protein unclassified drug DNA binding protein Drosophila protein hypoxia inducible factor 1alpha messenger RNA musashi protein, Drosophila protein binding RNA binding protein Sima protein, Drosophila 3' untranslated region animal cell animal tissue Article cell hypoxia controlled study down regulation Drosophila melanogaster embryo gene expression gene interaction insect cell culture mouse nonhuman priority journal protein protein interaction translation regulation animal biological model embryology gene locus genetic transcription genetics growth, development and aging mammal metabolism nucleotide sequence protein synthesis signal transduction trachea Animals Base Sequence DNA-Binding Proteins Down-Regulation Drosophila melanogaster Drosophila Proteins Genetic Loci Hypoxia-Inducible Factor 1, alpha Subunit Mammals Models, Biological Protein Binding Protein Biosynthesis RNA, Messenger RNA-Binding Proteins Signal Transduction Trachea Transcription, Genetic
description	Adaptation to hypoxia depends on a conserved α/β heterodimeric transcription factor called Hypoxia Inducible Factor (HIF), whose α-subunit is regulated by oxygen through different concurrent mechanisms. In this study, we have identified the RNA binding protein dMusashi, as a negative regulator of the fly HIF homologue Sima. Genetic interaction assays suggested that dMusashi participates of the HIF pathway, and molecular studies carried out in Drosophila cell cultures showed that dMusashi recognizes a Musashi Binding Element in the 3′ UTR of the HIFα transcript, thereby mediating its translational repression in normoxia. In hypoxic conditions dMusashi is downregulated, lifting HIFα repression and contributing to trigger HIF-dependent gene expression. Analysis performed in mouse brains revealed that murine Msi1 protein physically interacts with HIF-1α transcript, suggesting that the regulation of HIF by Msi might be conserved in mammalian systems. Thus, Musashi is a novel regulator of HIF that inhibits responses to hypoxia specifically when oxygen is available. © 2016 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research.
format	JOUR
author	Bertolin, A.P. Katz, M.J. Yano, M. Pozzi, B. Acevedo, J.M. Blanco-Obregón, D. Gándara, L. Sorianello, E. Kanda, H. Okano, H. Srebrow, A. Wappner, P.
author_facet	Bertolin, A.P. Katz, M.J. Yano, M. Pozzi, B. Acevedo, J.M. Blanco-Obregón, D. Gándara, L. Sorianello, E. Kanda, H. Okano, H. Srebrow, A. Wappner, P.
author_sort	Bertolin, A.P.
title	Musashi mediates translational repression of the Drosophila hypoxia inducible factor
title_short	Musashi mediates translational repression of the Drosophila hypoxia inducible factor
title_full	Musashi mediates translational repression of the Drosophila hypoxia inducible factor
title_fullStr	Musashi mediates translational repression of the Drosophila hypoxia inducible factor
title_full_unstemmed	Musashi mediates translational repression of the Drosophila hypoxia inducible factor
title_sort	musashi mediates translational repression of the drosophila hypoxia inducible factor
url	http://hdl.handle.net/20.500.12110/paper_03051048_v44_n16_p7555_Bertolin
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_version_	1807314776913608704

Musashi mediates translational repression of the Drosophila hypoxia inducible factor

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