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Specific inhibition of splicing factor activity by decoy RNA oligonucleotides

Author

Listed:
  • Polina Denichenko

    (Hebrew University-Hadassah Medical School)

  • Maxim Mogilevsky

    (Hebrew University-Hadassah Medical School)

  • Antoine Cléry

    (ETH Zurich)

  • Thomas Welte

    (GmbH)

  • Jakob Biran

    (Weizmann Institute of Science)

  • Odelia Shimshon

    (Hebrew University-Hadassah Medical School)

  • Georgina D. Barnabas

    (Tel Aviv University)

  • Miri Danan-Gotthold

    (Bar-Ilan University)

  • Saran Kumar

    (Hebrew University-Hadassah Medical School)

  • Eylon Yavin

    (Hebrew University-Hadassah Medical School)

  • Erez Y. Levanon

    (Bar-Ilan University)

  • Frédéric H. Allain

    (ETH Zurich)

  • Tamar Geiger

    (Tel Aviv University)

  • Gil Levkowitz

    (Weizmann Institute of Science)

  • Rotem Karni

    (Hebrew University-Hadassah Medical School)

Abstract

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.

Suggested Citation

  • Polina Denichenko & Maxim Mogilevsky & Antoine Cléry & Thomas Welte & Jakob Biran & Odelia Shimshon & Georgina D. Barnabas & Miri Danan-Gotthold & Saran Kumar & Eylon Yavin & Erez Y. Levanon & Frédéri, 2019. "Specific inhibition of splicing factor activity by decoy RNA oligonucleotides," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09523-0
    DOI: 10.1038/s41467-019-09523-0
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