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Michael Detmar - One of the best experts on this subject based on the ideXlab platform.
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identification of a human vpf vegf 3 Untranslated Region mediating hypoxia induced mrna stability
Molecular Biology of the Cell, 1998Co-Authors: Kevin P Claffey, Shuching Shih, Andrew Mullen, Suzan Dziennis, Jennifer L Cusick, Kristin Abrams, Michael DetmarAbstract:: 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.
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Identification of a Human VPF/VEGF 3′ Untranslated Region Mediating Hypoxia-induced mRNA Stability
Molecular Biology of the Cell, 1998Co-Authors: Kevin P Claffey, Shuching Shih, Andrew Mullen, Suzan Dziennis, Jennifer L Cusick, Kristin Abrams, Michael DetmarAbstract: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.
Chengyan He - One of the best experts on this subject based on the ideXlab platform.
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versican 3 Untranslated Region 3 utr functions as a cerna in inducing the development of hepatocellular carcinoma by regulating mirna activity
The FASEB Journal, 2013Co-Authors: Ling Fang, William W Du, Xiangling Yang, Kui Chen, Anand Ghanekar, G A Levy, Weining Yang, Weiyang Lu, Jim W Xuan, Chengyan HeAbstract:This study was designed to explore the role of versican in the development of hepatocellular carcinoma (HCC). Ectopic expression of the versican 3′-Untranslated Region (3′-UTR) was studied as a com...
Myriam Gorospe - One of the best experts on this subject based on the ideXlab platform.
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Differential Stability of Thymidylate Synthase 3-Untranslated Region Polymorphic Variants
2020Co-Authors: Rudolf Pullmann, Kotb Abdelmohsen, Jennifer L. Martindale, Robert D. Ladner, Myriam GorospeAbstract:A 6-nucleotide insertion (I)/deletion (D) polymorphism in the 3-Untranslated Region of the thymidylate synthase gene was shown to influence mRNA stability, but the molecular basis of this effect has not been elucidated. Here, studies of both endogenous and ectopically expressed thymidylate synthase alleles revealed that the mRNA-binding, decay-promoting protein AUF1 has higher affinity for allele D mRNA. AUF1 overexpression preferentially suppressed D allele mRNA levels, whereas AUF1 silencing selectively elevated D allele mRNA levels. Our results illustrate the functional consequences of ribonucleoprotein associations involving a polymorphic RNA sequence and uncover a novel mechanism of action for non-coding RNA polymorphisms.
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the trna methyltransferase nsun2 stabilizes p16ink mrna by methylating the 3 Untranslated Region of p16
Nature Communications, 2012Co-Authors: Xiaotian Zhang, Myriam Gorospe, Jie Yi, Hao Tang, Junyue Xing, Minqwei Yu, Tanjun Tong, Yongfeng Shang, Wengong WangAbstract:The expression of the tumour suppressor p16 is frequently lost in cancer. Zhang et al. show in cultured cells that p16 mRNA levels are stabilised by methylation of the 3′-Untranslated Region by the tRNA methyltransferase NSun2, revealing a new mechanism for regulating p16.
Ling Fang - One of the best experts on this subject based on the ideXlab platform.
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versican 3 Untranslated Region 3 utr functions as a cerna in inducing the development of hepatocellular carcinoma by regulating mirna activity
The FASEB Journal, 2013Co-Authors: Ling Fang, William W Du, Xiangling Yang, Kui Chen, Anand Ghanekar, G A Levy, Weining Yang, Weiyang Lu, Jim W Xuan, Chengyan HeAbstract:This study was designed to explore the role of versican in the development of hepatocellular carcinoma (HCC). Ectopic expression of the versican 3′-Untranslated Region (3′-UTR) was studied as a com...
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Versican 3′-Untranslated Region (3′-UTR) functions as a ceRNA in inducing the development of hepatocellular carcinoma by regulating miRNA activity
The FASEB Journal, 2012Co-Authors: Ling Fang, William W Du, Xiangling Yang, Kui Chen, Anand Ghanekar, G A Levy, Weining Yang, Weiyang Lu, Jim W XuanAbstract:This study was designed to explore the role of versican in the development of hepatocellular carcinoma (HCC). Ectopic expression of the versican 3′-Untranslated Region (3′-UTR) was studied as a com...
Oliver Muhlemann - One of the best experts on this subject based on the ideXlab platform.
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posttranscriptional gene regulation by spatial rearrangement of the 3 Untranslated Region
PLOS Biology, 2008Co-Authors: Andrea B Eberle, Lukas Stalder, Hansruedi Mathys, Rodolfo Zamudio Orozco, Oliver MuhlemannAbstract:Translation termination at premature termination codons (PTCs) triggers degradation of the aberrant mRNA, but the mechanism by which a termination event is defined as premature is still unclear. Here we show that the physical distance between the termination codon and the poly(A)-binding protein PABPC1 is a crucial determinant for PTC recognition in human cells. “Normal” termination codons can trigger nonsense-mediated mRNA decay (NMD) when this distance is extended; and vice versa, NMD can be suppressed by folding the poly(A) tail into proximity of a PTC or by tethering of PABPC1 nearby a PTC, indicating an evolutionarily conserved function of PABPC1 in promoting correct translation termination and antagonizing activation of NMD. Most importantly, our results demonstrate that spatial rearrangements of the 3′ Untranslated Region can modulate the NMD pathway and thereby provide a novel mechanism for posttranscriptional gene regulation.
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Posttranscriptional Gene Regulation by Spatial Rearrangement of the 3′ Untranslated Region
PLOS Biology, 2008Co-Authors: Andrea B Eberle, Lukas Stalder, Hansruedi Mathys, Rodolfo Zamudio Orozco, Oliver MuhlemannAbstract:Translation termination at premature termination codons (PTCs) triggers degradation of the aberrant mRNA, but the mechanism by which a termination event is defined as premature is still unclear. Here we show that the physical distance between the termination codon and the poly(A)-binding protein PABPC1 is a crucial determinant for PTC recognition in human cells. “Normal” termination codons can trigger nonsense-mediated mRNA decay (NMD) when this distance is extended; and vice versa, NMD can be suppressed by folding the poly(A) tail into proximity of a PTC or by tethering of PABPC1 nearby a PTC, indicating an evolutionarily conserved function of PABPC1 in promoting correct translation termination and antagonizing activation of NMD. Most importantly, our results demonstrate that spatial rearrangements of the 3′ Untranslated Region can modulate the NMD pathway and thereby provide a novel mechanism for posttranscriptional gene regulation.
