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mRNA Stability

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mRNA Stability - Free Register to Access Experts & Abstracts

Kevin P Claffey - One of the best experts on this subject based on the ideXlab platform.

  • double stranded rna binding protein regulates vascular endothelial growth factor mRNA Stability translation and breast cancer angiogenesis
    Molecular and Cellular Biology, 2008
    Co-Authors: Frank Vumbaca, Kathryn N Phoenix, Daniel Rodriguezpinto, David K Han, Kevin P Claffey
    Abstract:

    Vascular endothelial growth factor (VEGF) is a key angiogenic factor expressed under restricted nutrient and oxygen conditions in most solid tumors. The expression of VEGF under hypoxic conditions requires transcription through activated hypoxia-inducible factor 1 (HIF-1), increased mRNA Stability, and facilitated translation. This study identified double-stranded RNA-binding protein 76/NF90 (DRBP76/NF90), a specific isoform of the DRBP family, as a VEGF mRNA-binding protein which plays a key role in VEGF mRNA Stability and protein synthesis under hypoxia. The DRBP76/NF90 protein binds to a human VEGF 3' untranslated mRNA Stability element. RNA interference targeting the DRBP76/NF90 isoform limited hypoxia-inducible VEGF mRNA and protein expression with no change in HIF-1-dependent transcriptional activity. Stable repression of DRBP76/NF90 in MDA-MB-435 breast cancer cells demonstrated reduced polysome-associated VEGF mRNA levels under hypoxic conditions and reduced mRNA Stability. Transient overexpression of the DRBP76/NF90 protein increased both VEGF mRNA and protein levels synthesized under normoxic and hypoxic conditions. Cells with stable repression of the DRBP76/NF90 isoform showed reduced tumorigenic and angiogenic potential in an orthotopic breast tumor model. These data demonstrate that the DRBP76/NF90 isoform facilitates VEGF expression by promoting VEGF mRNA loading onto polysomes and translation under hypoxic conditions, thus promoting breast cancer growth and angiogenesis in vivo.

  • identification of a human vpf vegf 3 untranslated region mediating hypoxia induced mRNA Stability
    Molecular Biology of the Cell, 1998
    Co-Authors: Kevin P Claffey, Shuching Shih, Andrew Mullen, Suzan Dziennis, Jennifer L Cusick, Kristin Abrams, Michael Detmar
    Abstract:

    : Hypoxia is a prominent feature of malignant tumors that are characterized by angiogenesis and vascular hyperpermeability. Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) has been shown to be up-regulated in the vicinity of necrotic tumor areas, and hypoxia potently induces VPF/VEGF expression in several tumor cell lines in vitro. Here we report that hypoxia-induced VPF/VEGF expression is mediated by increased transcription and mRNA Stability in human M21 melanoma cells. RNA-binding/electrophoretic mobility shift assays identified a single 125-bp AU-rich element in the 3' untranslated region that formed hypoxia-inducible RNA-protein complexes. Hypoxia-induced expression of chimeric luciferase reporter constructs containing this 125-bp AU-rich hypoxia Stability region were significantly higher than constructs containing an adjacent 3' untranslated region element without RNA-binding activity. Using UV-cross-linking studies, we have identified a series of hypoxia-induced proteins of 90/88 kDa, 72 kDa, 60 kDa, 56 kDa, and 46 kDa that bound to the hypoxia Stability region element. The 90/88-kDa and 60-kDa species were specifically competed by excess hypoxia Stability region RNA. Thus, increased VPF/VEGF mRNA Stability induced by hypoxia is mediated, at least in part, by specific interactions between a defined mRNA Stability sequence in the 3' untranslated region and distinct mRNA-binding proteins in human tumor cells.

  • Identification of a Human VPF/VEGF 3′ Untranslated Region Mediating Hypoxia-induced mRNA Stability
    Molecular Biology of the Cell, 1998
    Co-Authors: Kevin P Claffey, Shuching Shih, Andrew Mullen, Suzan Dziennis, Jennifer L Cusick, Kristin Abrams, Michael Detmar
    Abstract:

    Hypoxia is a prominent feature of malignant tumors that are characterized by angiogenesis and vascular hyperpermeability. Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) has been shown to be up-regulated in the vicinity of necrotic tumor areas, and hypoxia potently induces VPF/VEGF expression in several tumor cell lines in vitro. Here we report that hypoxia-induced VPF/VEGF expression is mediated by increased transcription and mRNA Stability in human M21 melanoma cells. RNA-binding/electrophoretic mobility shift assays identified a single 125-bp AU-rich element in the 3' untranslated region that formed hypoxia-inducible RNA-protein complexes. Hypoxia-induced expression of chimeric luciferase reporter constructs containing this 125-bp AU-rich hypoxia Stability region were significantly higher than constructs containing an adjacent 3' untranslated region element without RNA-binding activity. Using UV-cross-linking studies, we have identified a series of hypoxia-induced proteins of 90/88 kDa, 72 kDa, 60 kDa, 56 kDa, and 46 kDa that bound to the hypoxia Stability region element. The 90/88-kDa and 60-kDa species were specifically competed by excess hypoxia Stability region RNA. Thus, increased VPF/VEGF mRNA Stability induced by hypoxia is mediated, at least in part, by specific interactions between a defined mRNA Stability sequence in the 3' untranslated region and distinct mRNA-binding proteins in human tumor cells.

Michael Detmar - One of the best experts on this subject based on the ideXlab platform.

  • identification of a human vpf vegf 3 untranslated region mediating hypoxia induced mRNA Stability
    Molecular Biology of the Cell, 1998
    Co-Authors: Kevin P Claffey, Shuching Shih, Andrew Mullen, Suzan Dziennis, Jennifer L Cusick, Kristin Abrams, Michael Detmar
    Abstract:

    : Hypoxia is a prominent feature of malignant tumors that are characterized by angiogenesis and vascular hyperpermeability. Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) has been shown to be up-regulated in the vicinity of necrotic tumor areas, and hypoxia potently induces VPF/VEGF expression in several tumor cell lines in vitro. Here we report that hypoxia-induced VPF/VEGF expression is mediated by increased transcription and mRNA Stability in human M21 melanoma cells. RNA-binding/electrophoretic mobility shift assays identified a single 125-bp AU-rich element in the 3' untranslated region that formed hypoxia-inducible RNA-protein complexes. Hypoxia-induced expression of chimeric luciferase reporter constructs containing this 125-bp AU-rich hypoxia Stability region were significantly higher than constructs containing an adjacent 3' untranslated region element without RNA-binding activity. Using UV-cross-linking studies, we have identified a series of hypoxia-induced proteins of 90/88 kDa, 72 kDa, 60 kDa, 56 kDa, and 46 kDa that bound to the hypoxia Stability region element. The 90/88-kDa and 60-kDa species were specifically competed by excess hypoxia Stability region RNA. Thus, increased VPF/VEGF mRNA Stability induced by hypoxia is mediated, at least in part, by specific interactions between a defined mRNA Stability sequence in the 3' untranslated region and distinct mRNA-binding proteins in human tumor cells.

  • Identification of a Human VPF/VEGF 3′ Untranslated Region Mediating Hypoxia-induced mRNA Stability
    Molecular Biology of the Cell, 1998
    Co-Authors: Kevin P Claffey, Shuching Shih, Andrew Mullen, Suzan Dziennis, Jennifer L Cusick, Kristin Abrams, Michael Detmar
    Abstract:

    Hypoxia is a prominent feature of malignant tumors that are characterized by angiogenesis and vascular hyperpermeability. Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) has been shown to be up-regulated in the vicinity of necrotic tumor areas, and hypoxia potently induces VPF/VEGF expression in several tumor cell lines in vitro. Here we report that hypoxia-induced VPF/VEGF expression is mediated by increased transcription and mRNA Stability in human M21 melanoma cells. RNA-binding/electrophoretic mobility shift assays identified a single 125-bp AU-rich element in the 3' untranslated region that formed hypoxia-inducible RNA-protein complexes. Hypoxia-induced expression of chimeric luciferase reporter constructs containing this 125-bp AU-rich hypoxia Stability region were significantly higher than constructs containing an adjacent 3' untranslated region element without RNA-binding activity. Using UV-cross-linking studies, we have identified a series of hypoxia-induced proteins of 90/88 kDa, 72 kDa, 60 kDa, 56 kDa, and 46 kDa that bound to the hypoxia Stability region element. The 90/88-kDa and 60-kDa species were specifically competed by excess hypoxia Stability region RNA. Thus, increased VPF/VEGF mRNA Stability induced by hypoxia is mediated, at least in part, by specific interactions between a defined mRNA Stability sequence in the 3' untranslated region and distinct mRNA-binding proteins in human tumor cells.

Huazhong Shi - One of the best experts on this subject based on the ideXlab platform.

  • Signaling control of SOS1 mRNA Stability
    Plant signaling & behavior, 2008
    Co-Authors: Jiafu Jiang, Huazhong Shi
    Abstract:

    Regulation of mRNA decay rates appears to be an important control point in determining the abundance of gene transcripts. Rapid change in decay rates of mRNAs could provide prompt responses of the plants to environmental fluctuations. SOS1 is a plasma-membrane Na+/H+ antiporter crucial for salt tolerance in Arabidopsis. In our recent paper in The Plant Journal, we have shown that SOS1 mRNA is inherently instable at normal growth conditions, but its Stability is substantially elevated by salt and oxidative stress treatments. Salt stress-induced SOS1 mRNA Stability is mediated by reactive oxygen species (ROS) produced, at least in part, through NADPH oxidases. We proposed a hypothetical model for the signaling pathway controlling SOS1 mRNA Stability. In this addendum, we discuss the possible involvement of other components in conferring inherent inStability and stress-induced Stability of SOS1 mRNA.

  • reactive oxygen species mediate na induced sos1 mRNA Stability in arabidopsis
    Plant Journal, 2007
    Co-Authors: Jung-sung Chung, Jian-kang Zhu, Ray A. Bressan, Paul M. Hasegawa, Huazhong Shi
    Abstract:

    *Summary Salt Overly Sensitive 1 (SOS1), a plasma membrane Na+ /H + antiporter in Arabidopsis, is a salt tolerance determinant crucial for the maintenance of ion homeostasis in saline stress conditions. SOS1 mRNA is unstable at normal growth conditions, but its Stability is substantially increased under salt stress and other ionic and dehydration stresses. In addition, H 2O2 treatment increases the Stability of SOS1 mRNA. SOS1 mRNA is inherently unstable and rapidly degraded with a half-life of approximately 10 min. Rapid decay of SOS1 mRNA requires new protein synthesis. Stress-induced SOS1 mRNA Stability is mediated by reactive oxygen species (ROS). NADPH oxidase is also involved in the upregulation of SOS1 mRNA Stability, presumably through the control of extracellular ROS production. The cis-element required for SOS1 mRNA inStability resides in the 500-bp region within the 2.2 kb at the 3¢ end of the SOS1 mRNA. Furthermore, mutations in the SOS1 gene render sos1 mutants more tolerant to paraquat, a non-selective herbicide causing oxidative stress, indicating that SOS1 plays negative roles in tolerance of oxidative stress. A hypothetical model for the signaling pathway involving SOS1-mediated pH changes, NADPH oxidase activation, apoplastic ROS production and downstream signaling transduction is proposed, and the biological significance of ROS-mediated induction of SOS1 mRNA Stability is discussed.

  • Reactive oxygen species mediate Na+-induced SOS1 mRNA Stability in Arabidopsis
    The Plant journal : for cell and molecular biology, 2007
    Co-Authors: Jung-sung Chung, Jian-kang Zhu, Ray A. Bressan, Paul M. Hasegawa, Huazhong Shi
    Abstract:

    *Summary Salt Overly Sensitive 1 (SOS1), a plasma membrane Na+ /H + antiporter in Arabidopsis, is a salt tolerance determinant crucial for the maintenance of ion homeostasis in saline stress conditions. SOS1 mRNA is unstable at normal growth conditions, but its Stability is substantially increased under salt stress and other ionic and dehydration stresses. In addition, H 2O2 treatment increases the Stability of SOS1 mRNA. SOS1 mRNA is inherently unstable and rapidly degraded with a half-life of approximately 10 min. Rapid decay of SOS1 mRNA requires new protein synthesis. Stress-induced SOS1 mRNA Stability is mediated by reactive oxygen species (ROS). NADPH oxidase is also involved in the upregulation of SOS1 mRNA Stability, presumably through the control of extracellular ROS production. The cis-element required for SOS1 mRNA inStability resides in the 500-bp region within the 2.2 kb at the 3¢ end of the SOS1 mRNA. Furthermore, mutations in the SOS1 gene render sos1 mutants more tolerant to paraquat, a non-selective herbicide causing oxidative stress, indicating that SOS1 plays negative roles in tolerance of oxidative stress. A hypothetical model for the signaling pathway involving SOS1-mediated pH changes, NADPH oxidase activation, apoplastic ROS production and downstream signaling transduction is proposed, and the biological significance of ROS-mediated induction of SOS1 mRNA Stability is discussed.

Andrew Mullen - One of the best experts on this subject based on the ideXlab platform.

  • identification of a human vpf vegf 3 untranslated region mediating hypoxia induced mRNA Stability
    Molecular Biology of the Cell, 1998
    Co-Authors: Kevin P Claffey, Shuching Shih, Andrew Mullen, Suzan Dziennis, Jennifer L Cusick, Kristin Abrams, Michael Detmar
    Abstract:

    : Hypoxia is a prominent feature of malignant tumors that are characterized by angiogenesis and vascular hyperpermeability. Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) has been shown to be up-regulated in the vicinity of necrotic tumor areas, and hypoxia potently induces VPF/VEGF expression in several tumor cell lines in vitro. Here we report that hypoxia-induced VPF/VEGF expression is mediated by increased transcription and mRNA Stability in human M21 melanoma cells. RNA-binding/electrophoretic mobility shift assays identified a single 125-bp AU-rich element in the 3' untranslated region that formed hypoxia-inducible RNA-protein complexes. Hypoxia-induced expression of chimeric luciferase reporter constructs containing this 125-bp AU-rich hypoxia Stability region were significantly higher than constructs containing an adjacent 3' untranslated region element without RNA-binding activity. Using UV-cross-linking studies, we have identified a series of hypoxia-induced proteins of 90/88 kDa, 72 kDa, 60 kDa, 56 kDa, and 46 kDa that bound to the hypoxia Stability region element. The 90/88-kDa and 60-kDa species were specifically competed by excess hypoxia Stability region RNA. Thus, increased VPF/VEGF mRNA Stability induced by hypoxia is mediated, at least in part, by specific interactions between a defined mRNA Stability sequence in the 3' untranslated region and distinct mRNA-binding proteins in human tumor cells.

  • Identification of a Human VPF/VEGF 3′ Untranslated Region Mediating Hypoxia-induced mRNA Stability
    Molecular Biology of the Cell, 1998
    Co-Authors: Kevin P Claffey, Shuching Shih, Andrew Mullen, Suzan Dziennis, Jennifer L Cusick, Kristin Abrams, Michael Detmar
    Abstract:

    Hypoxia is a prominent feature of malignant tumors that are characterized by angiogenesis and vascular hyperpermeability. Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) has been shown to be up-regulated in the vicinity of necrotic tumor areas, and hypoxia potently induces VPF/VEGF expression in several tumor cell lines in vitro. Here we report that hypoxia-induced VPF/VEGF expression is mediated by increased transcription and mRNA Stability in human M21 melanoma cells. RNA-binding/electrophoretic mobility shift assays identified a single 125-bp AU-rich element in the 3' untranslated region that formed hypoxia-inducible RNA-protein complexes. Hypoxia-induced expression of chimeric luciferase reporter constructs containing this 125-bp AU-rich hypoxia Stability region were significantly higher than constructs containing an adjacent 3' untranslated region element without RNA-binding activity. Using UV-cross-linking studies, we have identified a series of hypoxia-induced proteins of 90/88 kDa, 72 kDa, 60 kDa, 56 kDa, and 46 kDa that bound to the hypoxia Stability region element. The 90/88-kDa and 60-kDa species were specifically competed by excess hypoxia Stability region RNA. Thus, increased VPF/VEGF mRNA Stability induced by hypoxia is mediated, at least in part, by specific interactions between a defined mRNA Stability sequence in the 3' untranslated region and distinct mRNA-binding proteins in human tumor cells.

Kristin Abrams - One of the best experts on this subject based on the ideXlab platform.

  • identification of a human vpf vegf 3 untranslated region mediating hypoxia induced mRNA Stability
    Molecular Biology of the Cell, 1998
    Co-Authors: Kevin P Claffey, Shuching Shih, Andrew Mullen, Suzan Dziennis, Jennifer L Cusick, Kristin Abrams, Michael Detmar
    Abstract:

    : Hypoxia is a prominent feature of malignant tumors that are characterized by angiogenesis and vascular hyperpermeability. Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) has been shown to be up-regulated in the vicinity of necrotic tumor areas, and hypoxia potently induces VPF/VEGF expression in several tumor cell lines in vitro. Here we report that hypoxia-induced VPF/VEGF expression is mediated by increased transcription and mRNA Stability in human M21 melanoma cells. RNA-binding/electrophoretic mobility shift assays identified a single 125-bp AU-rich element in the 3' untranslated region that formed hypoxia-inducible RNA-protein complexes. Hypoxia-induced expression of chimeric luciferase reporter constructs containing this 125-bp AU-rich hypoxia Stability region were significantly higher than constructs containing an adjacent 3' untranslated region element without RNA-binding activity. Using UV-cross-linking studies, we have identified a series of hypoxia-induced proteins of 90/88 kDa, 72 kDa, 60 kDa, 56 kDa, and 46 kDa that bound to the hypoxia Stability region element. The 90/88-kDa and 60-kDa species were specifically competed by excess hypoxia Stability region RNA. Thus, increased VPF/VEGF mRNA Stability induced by hypoxia is mediated, at least in part, by specific interactions between a defined mRNA Stability sequence in the 3' untranslated region and distinct mRNA-binding proteins in human tumor cells.

  • Identification of a Human VPF/VEGF 3′ Untranslated Region Mediating Hypoxia-induced mRNA Stability
    Molecular Biology of the Cell, 1998
    Co-Authors: Kevin P Claffey, Shuching Shih, Andrew Mullen, Suzan Dziennis, Jennifer L Cusick, Kristin Abrams, Michael Detmar
    Abstract:

    Hypoxia is a prominent feature of malignant tumors that are characterized by angiogenesis and vascular hyperpermeability. Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) has been shown to be up-regulated in the vicinity of necrotic tumor areas, and hypoxia potently induces VPF/VEGF expression in several tumor cell lines in vitro. Here we report that hypoxia-induced VPF/VEGF expression is mediated by increased transcription and mRNA Stability in human M21 melanoma cells. RNA-binding/electrophoretic mobility shift assays identified a single 125-bp AU-rich element in the 3' untranslated region that formed hypoxia-inducible RNA-protein complexes. Hypoxia-induced expression of chimeric luciferase reporter constructs containing this 125-bp AU-rich hypoxia Stability region were significantly higher than constructs containing an adjacent 3' untranslated region element without RNA-binding activity. Using UV-cross-linking studies, we have identified a series of hypoxia-induced proteins of 90/88 kDa, 72 kDa, 60 kDa, 56 kDa, and 46 kDa that bound to the hypoxia Stability region element. The 90/88-kDa and 60-kDa species were specifically competed by excess hypoxia Stability region RNA. Thus, increased VPF/VEGF mRNA Stability induced by hypoxia is mediated, at least in part, by specific interactions between a defined mRNA Stability sequence in the 3' untranslated region and distinct mRNA-binding proteins in human tumor cells.