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Endogenous Multiple Exon Skipping and Back-Splicing at the DMD Mutation Hotspot
- Source :
- International Journal of Molecular Sciences, Vol 17, Iss 10, p 1722 (2016), International Journal of Molecular Sciences, International Journal of Molecular Sciences; Volume 17; Issue 10; Pages: 1722
- Publication Year :
- 2016
- Publisher :
- MDPI AG, 2016.
-
Abstract
- Duchenne muscular dystrophy (DMD) is a severe muscular disorder. It was reported that multiple exon skipping (MES), targeting exon 45–55 of the DMD gene, might improve patients’ symptoms because patients who have a genomic deletion of all these exons showed very mild symptoms. Thus, exon 45–55 skipping treatments for DMD have been proposed as a potential clinical cure. Herein, we detected the expression of endogenous exons 44–56 connected mRNA transcript of the DMD using total RNAs derived from human normal skeletal muscle by reverse transcription polymerase chain reaction (RT-PCR), and identified a total of eight types of MES products around the hotspot. Surprisingly, the 5′ splice sites of recently reported post-transcriptional introns (remaining introns after co-transcriptional splicing) act as splicing donor sites for MESs. We also tested exon combinations to generate DMD circular RNAs (circRNAs) and determined the preferential splice sites of back-splicing, which are involved not only in circRNA generation, but also in MESs. Our results fit the current circRNA-generation model, suggesting that upstream post-transcriptional introns trigger MES and generate circRNA because its existence is critical for the intra-intronic interaction or for extremely distal splicing.
- Subjects :
- 0301 basic medicine
Transcription, Genetic
RNA Splicing
Duchenne muscular dystrophy
pre-mRNA splicing
DMD
circular RNA
multiple exon skipping
Gene Expression
Biology
Exon shuffling
Article
Catalysis
Dystrophin
lcsh:Chemistry
Inorganic Chemistry
03 medical and health sciences
Exon
Circular RNA
RNA Precursors
medicine
Humans
RNA, Messenger
Physical and Theoretical Chemistry
lcsh:QH301-705.5
Molecular Biology
Spectroscopy
Genetics
Splice site mutation
Organic Chemistry
Intron
Exons
General Medicine
medicine.disease
Molecular biology
Exon skipping
Computer Science Applications
Muscular Dystrophy, Duchenne
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Mutation
RNA splicing
Subjects
Details
- ISSN :
- 14220067
- Volume :
- 17
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....7aad374883b67767233db07e0a693610