Specific inhibition of splicing factor activity by decoy RNA oligonucleotides.
Alternative Splicing
Animals
Animals, Genetically Modified
Binding Sites
Glioblastoma
/ genetics
HEK293 Cells
Heterogeneous-Nuclear Ribonucleoproteins
/ antagonists & inhibitors
Humans
MAP Kinase Signaling System
/ genetics
Muscle, Skeletal
/ growth & development
Nonsense Mediated mRNA Decay
Oligonucleotides
/ chemistry
Polypyrimidine Tract-Binding Protein
/ antagonists & inhibitors
RNA Splicing Factors
/ antagonists & inhibitors
Serine-Arginine Splicing Factors
/ antagonists & inhibitors
Tandem Repeat Sequences
Xenograft Model Antitumor Assays
Zebrafish
/ embryology
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 04 2019
08 04 2019
Historique:
received:
10
01
2018
accepted:
12
03
2019
entrez:
10
4
2019
pubmed:
10
4
2019
medline:
25
4
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30962446
doi: 10.1038/s41467-019-09523-0
pii: 10.1038/s41467-019-09523-0
pmc: PMC6453957
doi:
Substances chimiques
Heterogeneous-Nuclear Ribonucleoproteins
0
Oligonucleotides
0
PTBP1 protein, human
0
RBFOX1 protein, human
0
RNA Splicing Factors
0
SRSF1 protein, human
0
Polypyrimidine Tract-Binding Protein
139076-35-0
Serine-Arginine Splicing Factors
170974-22-8
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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