Endogenous Multiple Exon Skipping and Back-Splicing at the DMD Mutation Hotspot.
Int J Mol Sci
; 17(10)2016 Oct 13.
Article
em En
| MEDLINE
| ID: mdl-27754374
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.
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Base de dados:
MEDLINE
Assunto principal:
Precursores de RNA
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Splicing de RNA
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Éxons
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Distrofina
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Distrofia Muscular de Duchenne
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article