Specific inhibition of splicing factor activity by decoy RNA oligonucleotides

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, Frédéric H. Allain, Tamar Geiger, Gil Levkowitz, Rotem Karni*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number1590
JournalNature Communications
Volume10
Issue number1
DOIs
StatePublished - 1 Dec 2019

Fingerprint

Dive into the research topics of 'Specific inhibition of splicing factor activity by decoy RNA oligonucleotides'. Together they form a unique fingerprint.

Cite this