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A stress-responsive RNA switch regulates VEGF expression

Ligand binding to structural elements in noncoding regions of mRNA modulates gene expression1,2. Ligands such as free metabolites or other small molecules directly bind and induce conformational changes in regulatory RNA elements known as riboswitches1-4. Other types of RNA switches are activated by...

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Autores principales: Ray, Partho Sarothi, Jia, Jie, Yao, Peng, Majumder, Mithu, Hatzoglou, Maria, Fox, Paul L.
Formato: Texto
Lenguaje:English
Publicado: 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858559/
https://www.ncbi.nlm.nih.gov/pubmed/19098893
http://dx.doi.org/10.1038/nature07598
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author Ray, Partho Sarothi
Jia, Jie
Yao, Peng
Majumder, Mithu
Hatzoglou, Maria
Fox, Paul L.
author_facet Ray, Partho Sarothi
Jia, Jie
Yao, Peng
Majumder, Mithu
Hatzoglou, Maria
Fox, Paul L.
author_sort Ray, Partho Sarothi
collection PubMed
description Ligand binding to structural elements in noncoding regions of mRNA modulates gene expression1,2. Ligands such as free metabolites or other small molecules directly bind and induce conformational changes in regulatory RNA elements known as riboswitches1-4. Other types of RNA switches are activated by complexed metabolites, e.g., RNA-ligated metabolites such as aminoacyl-charged tRNA in the T-box system5, or protein-bound metabolites in the glucose- or amino acid-stimulated terminator-antiterminator systems6,7. All of these switch types are found in bacteria, fungi, and plants8-10. Here, we report an RNA switch in human vascular endothelial growth factor-A (VEGF) mRNA 3’UTR that integrates signals from interferon (IFN)-γ and hypoxia to regulate VEGF translation in myeloid cells. Analogous to riboswitches, the VEGF 3’UTR undergoes a binary conformational change in response to environmental signals. However, the VEGF 3’UTR switch is metabolite-independent, and the conformational change is dictated by mutually exclusive, stimulus-dependent binding of proteins, namely, the IFN-γ-activated inhibitor of translation (GAIT) complex11,12 and heterogenous nuclear ribonucleoprotein (hnRNP) L. We speculate the VEGF switch represents the founding member of a family of signal-mediated, protein-dependent RNA switches that evolved to regulate gene expression in multicellular animals where precise integration of disparate inputs may be more important than rapidity of response.
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spelling pubmed-28585592010-04-22 A stress-responsive RNA switch regulates VEGF expression Ray, Partho Sarothi Jia, Jie Yao, Peng Majumder, Mithu Hatzoglou, Maria Fox, Paul L. Nature Article Ligand binding to structural elements in noncoding regions of mRNA modulates gene expression1,2. Ligands such as free metabolites or other small molecules directly bind and induce conformational changes in regulatory RNA elements known as riboswitches1-4. Other types of RNA switches are activated by complexed metabolites, e.g., RNA-ligated metabolites such as aminoacyl-charged tRNA in the T-box system5, or protein-bound metabolites in the glucose- or amino acid-stimulated terminator-antiterminator systems6,7. All of these switch types are found in bacteria, fungi, and plants8-10. Here, we report an RNA switch in human vascular endothelial growth factor-A (VEGF) mRNA 3’UTR that integrates signals from interferon (IFN)-γ and hypoxia to regulate VEGF translation in myeloid cells. Analogous to riboswitches, the VEGF 3’UTR undergoes a binary conformational change in response to environmental signals. However, the VEGF 3’UTR switch is metabolite-independent, and the conformational change is dictated by mutually exclusive, stimulus-dependent binding of proteins, namely, the IFN-γ-activated inhibitor of translation (GAIT) complex11,12 and heterogenous nuclear ribonucleoprotein (hnRNP) L. We speculate the VEGF switch represents the founding member of a family of signal-mediated, protein-dependent RNA switches that evolved to regulate gene expression in multicellular animals where precise integration of disparate inputs may be more important than rapidity of response. 2008-12-21 2009-02-12 /pmc/articles/PMC2858559/ /pubmed/19098893 http://dx.doi.org/10.1038/nature07598 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Ray, Partho Sarothi
Jia, Jie
Yao, Peng
Majumder, Mithu
Hatzoglou, Maria
Fox, Paul L.
A stress-responsive RNA switch regulates VEGF expression
title A stress-responsive RNA switch regulates VEGF expression
title_full A stress-responsive RNA switch regulates VEGF expression
title_fullStr A stress-responsive RNA switch regulates VEGF expression
title_full_unstemmed A stress-responsive RNA switch regulates VEGF expression
title_short A stress-responsive RNA switch regulates VEGF expression
title_sort stress-responsive rna switch regulates vegf expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858559/
https://www.ncbi.nlm.nih.gov/pubmed/19098893
http://dx.doi.org/10.1038/nature07598
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