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Cryptic U2-dependent pre-mRNASplice site usage induced by splice switching antisense oligonucleotides
Research Square Preprints, Preprint
Research Square
2021
Abstract
Antisense oligomers (AOs) are increasingly being used for modulating RNA splicing in live cells, both for research and for therapeutic purposes. 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 such examples of AO-induced cryptic splice site activation – five new examples from our own experiments and three from reports published by others. We modelled the predicted effects that AO binding would have 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 a disruption to the exon definition signal within the exon’s excluded segment.
Details
- Title
- Cryptic U2-dependent pre-mRNASplice site usage induced by splice switching antisense oligonucleotides
- Authors/Creators
- K. Ham (Author/Creator)N. Keegan (Author/Creator)C. McIntosh (Author/Creator)M. Aung-Htut (Author/Creator)K. Zaw (Author/Creator)K. Greer (Author/Creator)S. Fletcher (Author/Creator)S. Wilton (Author/Creator)
- Publication Details
- Research Square Preprints, Preprint
- Publisher
- Research Square
- Identifiers
- 991005544507307891
- Murdoch Affiliation
- Centre for Molecular Medicine and Innovative Therapeutics; Health Futures Institute
- Language
- English
- Resource Type
- Other
- Resource Sub-type
- Nonrefereed Article
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