PUBLICATION
Specific inhibition of splicing factor activity by decoy RNA oligonucleotides
- Authors
- Denichenko, P., Mogilevsky, M., Cléry, A., Welte, T., Biran, J., Shimshon, O., Barnabas, G.D., Danan-Gotthold, M., Kumar, S., Yavin, E., Levanon, E.Y., Allain, F.H., Geiger, T., Levkowitz, G., Karni, R.
- ID
- ZDB-PUB-190425-2
- Date
- 2019
- Source
- Nature communications 10: 1590 (Journal)
- Registered Authors
- Biran, Jacob, Levkowitz, Gil
- Keywords
- none
- MeSH Terms
-
- Animals, Genetically Modified
- RNA Splicing Factors/antagonists & inhibitors
- RNA Splicing Factors/genetics*
- RNA Splicing Factors/metabolism
- Alternative Splicing
- Glioblastoma/genetics
- Glioblastoma/pathology
- Zebrafish/embryology
- Zebrafish/genetics
- Muscle, Skeletal/growth & development
- Polypyrimidine Tract-Binding Protein/antagonists & inhibitors
- Polypyrimidine Tract-Binding Protein/genetics*
- Polypyrimidine Tract-Binding Protein/metabolism
- HEK293 Cells
- Tandem Repeat Sequences
- Animals
- Binding Sites
- Oligonucleotides/chemistry
- Oligonucleotides/metabolism
- Oligonucleotides/pharmacology*
- Nonsense Mediated mRNA Decay
- MAP Kinase Signaling System/genetics
- Serine-Arginine Splicing Factors/antagonists & inhibitors
- Serine-Arginine Splicing Factors/genetics*
- Serine-Arginine Splicing Factors/metabolism
- Humans
- Heterogeneous-Nuclear Ribonucleoproteins/antagonists & inhibitors
- Heterogeneous-Nuclear Ribonucleoproteins/genetics*
- Heterogeneous-Nuclear Ribonucleoproteins/metabolism
- Xenograft Model Antitumor Assays
- PubMed
- 30962446 Full text @ Nat. Commun.
Citation
Denichenko, P., Mogilevsky, M., Cléry, A., Welte, T., Biran, J., Shimshon, O., Barnabas, G.D., Danan-Gotthold, M., Kumar, S., Yavin, E., Levanon, E.Y., Allain, F.H., Geiger, T., Levkowitz, G., Karni, R. (2019) Specific inhibition of splicing factor activity by decoy RNA oligonucleotides. Nature communications. 10:1590.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping