Specific inhibition of splicing factor activity by decoy RNA oligonucleotides.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30962446.
- Also identified by DOI 10.1038/s41467-019-09523-0 and PMC identifier 6453957.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Heterogeneous-Nuclear Ribonucleoproteins
- Oligonucleotides
- Polypyrimidine Tract-Binding Protein
- RNA Splicing Factors
- Serine-Arginine Splicing Factors