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We are analyzing https://www.nature.com/articles/s41467-019-09523-0.

Title:
Specific inhibition of splicing factor activity by decoy RNA oligonucleotides | Nature Communications
Description:
Alternative splicing, a fundamental step in gene expression, is deregulated in many diseases. Splicing factors (SFs), which regulate this process, are up- or down regulated or mutated in several diseases including cancer. To date, there are no inhibitors that directly inhibit the activity of SFs. We designed decoy oligonucleotides, composed of several repeats of a RNA motif, which is recognized by a single SF. Here we show that decoy oligonucleotides targeting splicing factors RBFOX1/2, SRSF1 and PTBP1, can specifically bind to their respective SFs and inhibit their splicing and biological activities both in vitro and in vivo. These decoy oligonucleotides present an approach to specifically downregulate SF activity in conditions where SFs are either up-regulated or hyperactive. Alternative splicing, critical for gene expression, is deregulated in many diseases. Here the authors develop decoy oligonucleotides to specifically downregulate splicing factors activity.
Website Age:
30 years and 10 months (reg. 1994-08-11).

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Keywords {🔍}

splicing, oligonucleotides, rbfox, cells, fig, decoy, article, srsf, google, scholar, supplementary, cas, rna, rbfoxi, data, binding, proteins, oligonucleotide, sfi, scrm, factors, factor, ptbp, cell, protein, alternative, cancer, transfected, targets, nature, analysis, inhibition, assay, motif, performed, specific, inhibit, rrm, experiments, represent, transfection, observed, activity, expression, bind, knockdown, control, means, results, effect,

Topics {✒️}

illumina library kits nature portfolio $${\mathrm{fb}}_{{\mathrm{eq}}}\left privacy policy matrix-assisted laser desorption/ionization nature communications serum-resistant cpg-stat3 decoy medical research israel-canada advertising supplementary movie 1 hrp-conjugated goat anti-mouse prepare libraries reporting summary splicing factor sf2/asf isolated pseudo-rna-recognition motifs supplementary information files solutions reprints data represent means ± sd full size image nature 499 nature 463 nature replicate rna-seq data aptamer-based targeted therapy donkey anti-goat igg electro-switchable dna chip anti-tumor effects nathan ptb-rna interactions reveals nis–elements br software mitogen-activated protein kinases dna/rna chimeric molecule lc/ms sample pretreatment nonsense mediated decay possess rna-independent functions impacts ras-induced transformation purine-rich rna recognition author information authors modulate exon inclusion p38-mapk stress pathway43 dna/rna chimeric molecules endogenous nmd-prone transcripts48 rna-binding motifs interacts rna binding-independent manner21 scatter plot showing mapping rna-protein interactions p38-mapk stress pathway mek1-mapk-erk activation rbfox2-coordinated alternative splicing aberrant pre-mrna splicing

Questions {❓}

  • Targeting RNA splicing modulation: new perspectives for anticancer strategy?

Schema {🗺️}

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         description:Alternative splicing, a fundamental step in gene expression, is deregulated in many diseases. Splicing factors (SFs), which regulate this process, are up- or down regulated or mutated in several diseases including cancer. To date, there are no inhibitors that directly inhibit the activity of SFs. We designed decoy oligonucleotides, composed of several repeats of a RNA motif, which is recognized by a single SF. Here we show that decoy oligonucleotides targeting splicing factors RBFOX1/2, SRSF1 and PTBP1, can specifically bind to their respective SFs and inhibit their splicing and biological activities both in vitro and in vivo. These decoy oligonucleotides present an approach to specifically downregulate SF activity in conditions where SFs are either up-regulated or hyperactive. Alternative splicing, critical for gene expression, is deregulated in many diseases. Here the authors develop decoy oligonucleotides to specifically downregulate splicing factors activity.
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      headline:Specific inhibition of splicing factor activity by decoy RNA oligonucleotides
      description:Alternative splicing, a fundamental step in gene expression, is deregulated in many diseases. Splicing factors (SFs), which regulate this process, are up- or down regulated or mutated in several diseases including cancer. To date, there are no inhibitors that directly inhibit the activity of SFs. We designed decoy oligonucleotides, composed of several repeats of a RNA motif, which is recognized by a single SF. Here we show that decoy oligonucleotides targeting splicing factors RBFOX1/2, SRSF1 and PTBP1, can specifically bind to their respective SFs and inhibit their splicing and biological activities both in vitro and in vivo. These decoy oligonucleotides present an approach to specifically downregulate SF activity in conditions where SFs are either up-regulated or hyperactive. Alternative splicing, critical for gene expression, is deregulated in many diseases. Here the authors develop decoy oligonucleotides to specifically downregulate splicing factors activity.
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            type:Organization
      name:Jakob Biran
      affiliation:
            name:Weizmann Institute of Science
            address:
               name:Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
               type:PostalAddress
            type:Organization
      name:Odelia Shimshon
      affiliation:
            name:Hebrew University-Hadassah Medical School
            address:
               name:Department of Medicinal Chemistry, Institute for Drug Research, Hebrew University-Hadassah Medical School, Jerusalem, Israel
               type:PostalAddress
            type:Organization
      name:Georgina D. Barnabas
      affiliation:
            name:Tel Aviv University
            address:
               name:Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
               type:PostalAddress
            type:Organization
      name:Miri Danan-Gotthold
      affiliation:
            name:Bar-Ilan University
            address:
               name:Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel
               type:PostalAddress
            type:Organization
      name:Saran Kumar
      url:http://orcid.org/0000-0002-5052-0499
      affiliation:
            name:Hebrew University-Hadassah Medical School
            address:
               name:Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, Hebrew University-Hadassah Medical School, Jerusalem, Israel
               type:PostalAddress
            type:Organization
      name:Eylon Yavin
      affiliation:
            name:Hebrew University-Hadassah Medical School
            address:
               name:Department of Medicinal Chemistry, Institute for Drug Research, Hebrew University-Hadassah Medical School, Jerusalem, Israel
               type:PostalAddress
            type:Organization
      name:Erez Y. Levanon
      url:http://orcid.org/0000-0002-3641-4198
      affiliation:
            name:Bar-Ilan University
            address:
               name:Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel
               type:PostalAddress
            type:Organization
      name:Frédéric H. Allain
      affiliation:
            name:ETH Zurich
            address:
               name:Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland
               type:PostalAddress
            type:Organization
      name:Tamar Geiger
      affiliation:
            name:Tel Aviv University
            address:
               name:Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
               type:PostalAddress
            type:Organization
      name:Gil Levkowitz
      url:http://orcid.org/0000-0002-3896-1881
      affiliation:
            name:Weizmann Institute of Science
            address:
               name:Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
               type:PostalAddress
            type:Organization
      name:Rotem Karni
      url:http://orcid.org/0000-0002-7552-9617
      affiliation:
            name:Hebrew University-Hadassah Medical School
            address:
               name:Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel
      name:Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel
      name:Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland
      name:Dynamic Biosensors, GmbH, Martinsried/Planegg, Germany
      name:Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
      name:Department of Medicinal Chemistry, Institute for Drug Research, Hebrew University-Hadassah Medical School, Jerusalem, Israel
      name:Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
      name:Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel
      name:Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, Hebrew University-Hadassah Medical School, Jerusalem, Israel
      name:Department of Medicinal Chemistry, Institute for Drug Research, Hebrew University-Hadassah Medical School, Jerusalem, Israel
      name:Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan, Israel
      name:Institute of Molecular Biology and Biophysics, ETH Zurich, Zurich, Switzerland
      name:Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
      name:Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
      name:Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel

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