The Experts below are selected from a list of 2688 Experts worldwide ranked by ideXlab platform
Kuniyoshi Shimizu - One of the best experts on this subject based on the ideXlab platform.
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Ursolic Acid Isolated from the Leaves of Loquat ( Eriobotrya japonica) Inhibited Osteoclast Differentiation through Targeting Exportin 5.
Journal of agricultural and food chemistry, 2019Co-Authors: Hui Tan, Koichiro Ohnuki, Chong Zhao, Qinchang Zhu, Yoshinori Katakura, Hiroyuki Tanaka, Kuniyoshi ShimizuAbstract:One of the conventional strategies for treating osteoporosis is to eliminate the multinucleated osteoclasts that are responsible for bone resorption. Our previous study revealed that ursolic acid, isolated from leaves of loquat that is used as tasty tea in Japan, suppressed osteoclastogenesis. We confirmed that ursolic acid exhibited osteoclast differentiation inhibitory activity with an 50% inhibitory concentration (IC50) value of 5.4 ± 0.96 μM. To disclose its mechanism of action, this study first uses polymer-coated magnetic nanobeads to identify potential target proteins. As a result, we identified a nuclear exporter protein named Exportin 5 (XPO5). Further studies demonstrated that knockdown of XPO5 significantly blocks osteoclast differentiation ( P < 0.01). Expression profiling of mature microRNAs in the cells revealed that downregulation of XPO5 by small interfering RNA or by ursolic acid could downregulate the expression of mature microRNA let-7g-5p during osteoclast differentiation ( P < 0.01). Collectively, our findings suggest that ursolic acid inhibits osteoclast differentiation through targeting XPO5, which provides further evidence for the healthy function of the tea. This study also provides new insights into the role of XPO5 and its mediated microRNAs in treatment for bone resorption diseases.
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Ursolic Acid Isolated from the Leaves of Loquat (Eriobotrya japonica) Inhibited Osteoclast Differentiation through Targeting Exportin 5
2019Co-Authors: Hui Tan, Koichiro Ohnuki, Chong Zhao, Qinchang Zhu, Yoshinori Katakura, Hiroyuki Tanaka, Kuniyoshi ShimizuAbstract:One of the conventional strategies for treating osteoporosis is to eliminate the multinucleated osteoclasts that are responsible for bone resorption. Our previous study revealed that ursolic acid, isolated from leaves of loquat that is used as tasty tea in Japan, suppressed osteoclastogenesis. We confirmed that ursolic acid exhibited osteoclast differentiation inhibitory activity with an 50% inhibitory concentration (IC50) value of 5.4 ± 0.96 μM. To disclose its mechanism of action, this study first uses polymer-coated magnetic nanobeads to identify potential target proteins. As a result, we identified a nuclear exporter protein named Exportin 5 (XPO5). Further studies demonstrated that knockdown of XPO5 significantly blocks osteoclast differentiation (P < 0.01). Expression profiling of mature microRNAs in the cells revealed that downregulation of XPO5 by small interfering RNA or by ursolic acid could downregulate the expression of mature microRNA let-7g-5p during osteoclast differentiation (P < 0.01). Collectively, our findings suggest that ursolic acid inhibits osteoclast differentiation through targeting XPO5, which provides further evidence for the healthy function of the tea. This study also provides new insights into the role of XPO5 and its mediated microRNAs in treatment for bone resorption diseases
Matheus De Souza Gomes - One of the best experts on this subject based on the ideXlab platform.
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differential expression of small rna pathway genes associated with the biomphalaria glabrata schistosoma mansoni interaction
PLOS ONE, 2017Co-Authors: Fábio Ribeiro Queiroz, Luciana Maria Silva, Wander De Jesus Jeremias, Élio Hideo Babá, Roberta Lima Caldeira, Paulo Marcos Zech Coelho, Matheus De Souza GomesAbstract:The World Health Organization (WHO) estimates that approximately 240 million people in 78 countries require treatment for schistosomiasis, an endemic disease caused by trematodes of the genus Schistosoma. In Brazil, Schistosoma mansoni is the only species representative of the genus whose passage through an invertebrate host, snails of the genus Biomphalaria, is obligatory before infecting a mammalian host, including humans. The availability of the genome and transcriptome of B. glabrata makes studying the regulation of gene expression, particularly the regulation of miRNA and piRNA processing pathway genes, possible. This might assist in better understanding the biology of B. glabrata as well as its relationship to the parasite S. mansoni. Some aspects of this interaction are still poorly explored, including the participation of non-coding small RNAs, such as miRNAs and piRNAs, with lengths varying from 18 to 30 nucleotides in mature form, which are potent regulators of gene expression. Using bioinformatics tools and quantitative PCR, we characterized and validated the miRNA and piRNA processing pathway genes in B. glabrata. In silico analyses showed that genes involved in miRNA and piRNA pathways were highly conserved in protein domain distribution, catalytic site residue conservation and phylogenetic analysis. Our study showed differential expression of putative Argonaute, Drosha, Piwi, Exportin-5 and Tudor genes at different snail developmental stages and during infection with S. mansoni, suggesting that the machinery is required for miRNA and piRNA processing in B. glabrata at all stages. These data suggested that the silencing pathway mediated by miRNAs and piRNAs can interfere in snail biology throughout the life cycle of the snail, thereby influencing the B. glabrata/S. mansoni interaction. Further studies are needed to confirm the participation of the small RNA processing pathway proteins in the parasite/host relationship, mainly the effective participation of small RNAs in regulating their target genes.
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Relative gene expression of B. glabrata at several time points of infection by S. mansoni using uninfected snails at the same time points as a baseline.
2017Co-Authors: Fábio Ribeiro Queiroz, Luciana Maria Silva, Wander De Jesus Jeremias, Élio Hideo Babá, Roberta Lima Caldeira, Paulo Marcos Zech Coelho, Matheus De Souza GomesAbstract:A—Argonaute was significantly down-regulated 4 hours after infection compared to 24 hours, 7 days and 21 days after infection; B—Piwi was significantly down-regulated at 4 hours compared to 24 hours and 7 days but was significantly up-regulated at 7 days compared to 15 days; C—Drosha was significantly down-regulated at 4 hours compared to 12 hours and 7 days but was significantly up-regulated at 7 days compared to 30 days; D—Exportin-5 was significantly down-regulated at 4 hours compared to 7 days and 21 days; and significantly up-regulated at 21 days compared to 15 and 30 days; E—Tudor was significantly down-regulated at 4 hours compared to 24 hours and significantly down-regulated at 12 hours compared to 24 hours and 30 days.
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Differential expression of small RNA pathway genes associated with the Biomphalaria glabrata/Schistosoma mansoni interaction
2017Co-Authors: Fábio Ribeiro Queiroz, Luciana Maria Silva, Wander De Jesus Jeremias, Élio Hideo Babá, Roberta Lima Caldeira, Paulo Marcos Zech Coelho, Matheus De Souza GomesAbstract:The World Health Organization (WHO) estimates that approximately 240 million people in 78 countries require treatment for schistosomiasis, an endemic disease caused by trematodes of the genus Schistosoma. In Brazil, Schistosoma mansoni is the only species representative of the genus whose passage through an invertebrate host, snails of the genus Biomphalaria, is obligatory before infecting a mammalian host, including humans. The availability of the genome and transcriptome of B. glabrata makes studying the regulation of gene expression, particularly the regulation of miRNA and piRNA processing pathway genes, possible. This might assist in better understanding the biology of B. glabrata as well as its relationship to the parasite S. mansoni. Some aspects of this interaction are still poorly explored, including the participation of non-coding small RNAs, such as miRNAs and piRNAs, with lengths varying from 18 to 30 nucleotides in mature form, which are potent regulators of gene expression. Using bioinformatics tools and quantitative PCR, we characterized and validated the miRNA and piRNA processing pathway genes in B. glabrata. In silico analyses showed that genes involved in miRNA and piRNA pathways were highly conserved in protein domain distribution, catalytic site residue conservation and phylogenetic analysis. Our study showed differential expression of putative Argonaute, Drosha, Piwi, Exportin-5 and Tudor genes at different snail developmental stages and during infection with S. mansoni, suggesting that the machinery is required for miRNA and piRNA processing in B. glabrata at all stages. These data suggested that the silencing pathway mediated by miRNAs and piRNAs can interfere in snail biology throughout the life cycle of the snail, thereby influencing the B. glabrata/S. mansoni interaction. Further studies are needed to confirm the participation of the small RNA processing pathway proteins in the parasite/host relationship, mainly the effective participation of small RNAs in regulating their target genes.
Dirk Gorlich - One of the best experts on this subject based on the ideXlab platform.
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Exportin 5 is a rangtp dependent dsrna binding protein that mediates nuclear export of pre mirnas
RNA, 2004Co-Authors: Markus T Bohnsack, Kevin Czaplinski, Dirk GorlichAbstract:microRNAs (miRNAs) are widespread among eukaryotes, and studies in several systems have revealed that miRNAs can regulate expression of specific genes. Primary miRNA transcripts are initially processed to � 70-nucleotide (nt) stem–loop structures (pre-miRNAs), exported to the cytoplasm, further processed to yield � 22-nt dsRNAs, and finally incorporated into ribonucleoprotein particles, which are thought to be the active species. Here we study nuclear export of pre-miRNAs and show that the process is saturable and thus carrier-mediated. Export is sensitive to depletion of nuclear RanGTP and, according to this criterion, mediated by a RanGTP-dependent Exportin. An unbiased affinity chromatography approach with immobilized pre-miRNAs identified Exportin 5 as the pre-miRNA-specific export carrier. We have cloned Exportin 5 from Xenopus and demonstrate that antibodies raised against the Xenopus receptor specifically block pre-miRNA export from nuclei of Xenopus oocytes. We further show that Exportin 5 interacts with double-stranded RNA in a sequence-independent manner.
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Exportin 5 is a rangtp dependent dsrna binding protein that mediates nuclear export of pre mirnas
RNA, 2004Co-Authors: Markus T Bohnsack, Kevin Czaplinski, Dirk GorlichAbstract:microRNAs (miRNAs) are widespread among eukaryotes, and studies in several systems have revealed that miRNAs can regulate expression of specific genes. Primary miRNA transcripts are initially processed to approximately 70-nucleotide (nt) stem-loop structures (pre-miRNAs), exported to the cytoplasm, further processed to yield approximately 22-nt dsRNAs, and finally incorporated into ribonucleoprotein particles, which are thought to be the active species. Here we study nuclear export of pre-miRNAs and show that the process is saturable and thus carrier-mediated. Export is sensitive to depletion of nuclear RanGTP and, according to this criterion, mediated by a RanGTP-dependent Exportin. An unbiased affinity chromatography approach with immobilized pre-miRNAs identified Exportin 5 as the pre-miRNA-specific export carrier. We have cloned Exportin 5 from Xenopus and demonstrate that antibodies raised against the Xenopus receptor specifically block pre-miRNA export from nuclei of Xenopus oocytes. We further show that Exportin 5 interacts with double-stranded RNA in a sequence-independent manner.
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exp5 exports eef1a via trna from nuclei and synergizes with other transport pathways to confine translation to the cytoplasm
The EMBO Journal, 2002Co-Authors: Markus T Bohnsack, Kathrin Regener, Blanche Schwappach, Rainer Saffrich, Efrosyni Paraskeva, Enno Hartmann, Dirk GorlichAbstract:Importin β-type transport receptors mediate the vast majority of transport pathways between cell nucleus and cytoplasm. We identify here the translation elongation factor 1A (eEF1A) as the predominant nuclear export substrate of RanBP21/Exportin 5 (Exp5). This cargo–Exportin interaction is rather un usual in that eEF1A binds the Exportin not directly, but instead via aminoacylated tRNAs. Exp5 thus represents the second directly RNA-binding Exportin and mediates tRNA export in parallel with Exportin-t. It was suggested recently that 10–15% of the cellular translation would occur in the nucleus. Our data rule out such a scenario and instead suggest that nuclear translation is actively suppressed by the nuclear export machinery. We found that the vast majority of translation initiation factors (eIF2, eIF2B, eIF3, eIF4A1, eIF5 and eIF5B), all three elongation factors (eEF1A, eEF1B and eEF2) and the termination factor eRF1 are strictly excluded from nuclei. Besides Exp5 and importin 13, CRM1 and as yet unidentified Exportins also contribute to the depletion of translation factors from nuclei.
Hui Tan - One of the best experts on this subject based on the ideXlab platform.
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Ursolic Acid Isolated from the Leaves of Loquat ( Eriobotrya japonica) Inhibited Osteoclast Differentiation through Targeting Exportin 5.
Journal of agricultural and food chemistry, 2019Co-Authors: Hui Tan, Koichiro Ohnuki, Chong Zhao, Qinchang Zhu, Yoshinori Katakura, Hiroyuki Tanaka, Kuniyoshi ShimizuAbstract:One of the conventional strategies for treating osteoporosis is to eliminate the multinucleated osteoclasts that are responsible for bone resorption. Our previous study revealed that ursolic acid, isolated from leaves of loquat that is used as tasty tea in Japan, suppressed osteoclastogenesis. We confirmed that ursolic acid exhibited osteoclast differentiation inhibitory activity with an 50% inhibitory concentration (IC50) value of 5.4 ± 0.96 μM. To disclose its mechanism of action, this study first uses polymer-coated magnetic nanobeads to identify potential target proteins. As a result, we identified a nuclear exporter protein named Exportin 5 (XPO5). Further studies demonstrated that knockdown of XPO5 significantly blocks osteoclast differentiation ( P < 0.01). Expression profiling of mature microRNAs in the cells revealed that downregulation of XPO5 by small interfering RNA or by ursolic acid could downregulate the expression of mature microRNA let-7g-5p during osteoclast differentiation ( P < 0.01). Collectively, our findings suggest that ursolic acid inhibits osteoclast differentiation through targeting XPO5, which provides further evidence for the healthy function of the tea. This study also provides new insights into the role of XPO5 and its mediated microRNAs in treatment for bone resorption diseases.
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Ursolic Acid Isolated from the Leaves of Loquat (Eriobotrya japonica) Inhibited Osteoclast Differentiation through Targeting Exportin 5
2019Co-Authors: Hui Tan, Koichiro Ohnuki, Chong Zhao, Qinchang Zhu, Yoshinori Katakura, Hiroyuki Tanaka, Kuniyoshi ShimizuAbstract:One of the conventional strategies for treating osteoporosis is to eliminate the multinucleated osteoclasts that are responsible for bone resorption. Our previous study revealed that ursolic acid, isolated from leaves of loquat that is used as tasty tea in Japan, suppressed osteoclastogenesis. We confirmed that ursolic acid exhibited osteoclast differentiation inhibitory activity with an 50% inhibitory concentration (IC50) value of 5.4 ± 0.96 μM. To disclose its mechanism of action, this study first uses polymer-coated magnetic nanobeads to identify potential target proteins. As a result, we identified a nuclear exporter protein named Exportin 5 (XPO5). Further studies demonstrated that knockdown of XPO5 significantly blocks osteoclast differentiation (P < 0.01). Expression profiling of mature microRNAs in the cells revealed that downregulation of XPO5 by small interfering RNA or by ursolic acid could downregulate the expression of mature microRNA let-7g-5p during osteoclast differentiation (P < 0.01). Collectively, our findings suggest that ursolic acid inhibits osteoclast differentiation through targeting XPO5, which provides further evidence for the healthy function of the tea. This study also provides new insights into the role of XPO5 and its mediated microRNAs in treatment for bone resorption diseases
Ulrike Kutay - One of the best experts on this subject based on the ideXlab platform.
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a protein inventory of human ribosome biogenesis reveals an essential function of Exportin 5 in 60s subunit export
PLOS Biology, 2010Co-Authors: Thomas Wild, Elsebet Lund, Peter Horvath, Emanuel Wyler, Barbara Widmann, Lukas Badertscher, Ivo Zemp, Karol Kozak, Gabor Csucs, Ulrike KutayAbstract:The assembly of ribosomal subunits in eukaryotes is a complex, multistep process so far mostly studied in yeast. In S. cerevisiae, more than 200 factors including ribosomal proteins and trans-acting factors are required for the ordered assembly of 40S and 60S ribosomal subunits. To date, only few human homologs of these yeast ribosome synthesis factors have been characterized. Here, we used a systematic RNA interference (RNAi) approach to analyze the contribution of 464 candidate factors to ribosomal subunit biogenesis in human cells. The screen was based on visual readouts, using inducible, fluorescent ribosomal proteins as reporters. By performing computer-based image analysis utilizing supervised machine-learning techniques, we obtained evidence for a functional link of 153 human proteins to ribosome synthesis. Our data show that core features of ribosome assembly are conserved from yeast to human, but differences exist for instance with respect to 60S subunit export. Unexpectedly, our RNAi screen uncovered a requirement for the export receptor Exportin 5 (Exp5) in nuclear export of 60S subunits in human cells. We show that Exp5, like the known 60S Exportin Crm1, binds to pre-60S particles in a RanGTP-dependent manner. Interference with either Exp5 or Crm1 function blocks 60S export in both human cells and frog oocytes, whereas 40S export is compromised only upon inhibition of Crm1. Thus, 60S subunit export is dependent on at least two RanGTP-binding Exportins in vertebrate cells.
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Nuclear Export of MicroRNA Precursors
Science, 2004Co-Authors: Elsebet Lund, Stephan Güttinger, Angelo Calado, James E. Dahlberg, Ulrike KutayAbstract:MicroRNAs (miRNAs), which function as regulators of gene expression in eukaryotes, are processed from larger transcripts by sequential action of nuclear and cytoplasmic ribonuclease III-like endonucleases. We show that Exportin-5 (Exp5) mediates efficient nuclear export of short miRNA precursors (pre-miRNAs) and that its depletion by RNA interference results in reduced miRNA levels. Exp5 binds correctly processed pre-miRNAs directly and specifically, in a Ran guanosine triphosphate-dependent manner, but interacts only weakly with extended pre-miRNAs that yield incorrect miRNAs when processed by Dicer in vitro. Thus, Exp5 is key to miRNA biogenesis and may help coordinate nuclear and cytoplasmic processing steps.
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Exportin 5 mediated nuclear export of eukaryotic elongation factor 1a and trna
The EMBO Journal, 2002Co-Authors: Nathalie Treichel, Angelo Calado, Evachristina Muller, Albrecht Otto, Ulrike KutayAbstract:Transport of proteins and RNA into and out of the cell nucleus is mediated largely by a family of RanGTP-binding transport receptors. Export receptors (Exportins) need to bind RanGTP for efficient loading of their export cargo. We have identified eukaryotic elongation factor 1A (eEF1A) and tRNA as RanGTP-dependent binding partners of Exportin-5 (Exp5). Exp5 stimulates nuclear export of eEF1A when microinjected into the nucleus of Xenopus laevis oocytes. Surprisingly, the interaction between eEF1A and Exp5 is dependent on tRNA that can interact directly with Exp5 and, if aminoacylated, recruits eEF1A into the export complex. These data suggested to us that Exp5 might support tRNA export. Indeed, not only the canonical tRNA export receptor, Exportin-t, but also Exp5 can drive nuclear export of tRNA. Taken together, we show that there exists an alternative tRNA export pathway which can be exploited to keep eEF1A out of the cell nucleus.
