Publication: Induction of cryptic pre-mRNA splice-switching by antisense oligonucleotides
Issued Date
2021-12-01
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ISSN
20452322
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2-s2.0-85111091438
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Mahidol University
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SCOPUS
Bibliographic Citation
Scientific Reports. Vol.11, No.1 (2021)
Suggested Citation
Kristin A. Ham, Niall P. Keegan, Craig S. McIntosh, May T. Aung-Htut, Khine Zaw, Kane Greer, Sue Fletcher, Steve D. Wilton Induction of cryptic pre-mRNA splice-switching by antisense oligonucleotides. Scientific Reports. Vol.11, No.1 (2021). doi:10.1038/s41598-021-94639-x Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/79225
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Title
Induction of cryptic pre-mRNA splice-switching by antisense oligonucleotides
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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.
