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Journal article
Induction of cryptic pre-mRNA splice-switching by antisense oligonucleotides
Scientific Reports, Vol.11(1), Article 15137
2021
Abstract
Antisense oligomers (AOs) are increasingly being used to modulate RNA splicing in live cells, both for research and for the development of therapeutics. While the most common intended effect of these AOs is to induce skipping of whole exons, rare examples are emerging of AOs that induce skipping of only part of an exon, through activation of an internal cryptic splice site. In this report, we examined seven AO-induced cryptic splice sites in six genes. Five of these cryptic splice sites were discovered through our own experiments, and two originated from other published reports. We modelled the predicted effects of AO binding on the secondary structure of each of the RNA targets, and how these alterations would in turn affect the accessibility of the RNA to splice factors. We observed that a common predicted effect of AO binding was disruption of the exon definition signal within the exon’s excluded segment.
Details
- Title
- Induction of cryptic pre-mRNA splice-switching by antisense oligonucleotides
- Authors/Creators
- K.A. Ham (Author/Creator) - Murdoch UniversityN.P. Keegan (Author/Creator) - Murdoch UniversityC.S. McIntosh (Author/Creator) - Murdoch UniversityM.T. Aung-Htut (Author/Creator) - Murdoch UniversityK. Zaw (Author/Creator) - Murdoch UniversityK. Greer (Author/Creator) - Murdoch UniversityS. Fletcher (Author/Creator) - Murdoch UniversityS.D. Wilton (Author/Creator) - Murdoch University
- Publication Details
- Scientific Reports, Vol.11(1), Article 15137
- Publisher
- Springer Nature
- Identifiers
- 991005541274407891
- Copyright
- © 2021 The Authors
- Murdoch Affiliation
- Centre for Molecular Medicine and Innovative Therapeutics; Health Futures Institute
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.54 Molecular & Cell Biology - Genetics
- 1.54.469 Alternative Splicing
- Web Of Science research areas
- Biochemistry & Molecular Biology
- ESI research areas
- Molecular Biology & Genetics