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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.
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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?
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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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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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