Endogenous multiple exon skipping and back-splicing at the DMD mutation hotspot

Hitoshi Suzuki, Yoshitsugu Aoki, Toshiki Kameyama, Takashi Saito, Satoru Masuda, Jun Tanihata, Tetsuya Nagata, Akila Mayeda, Shin’Ichi Takeda, Toshifumi Tsukahara

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21 Citations (Scopus)

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 50 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.

Original languageEnglish
Article number1722
JournalInternational journal of molecular sciences
Volume17
Issue number10
DOIs
Publication statusPublished - 13-10-2016

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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    Suzuki, H., Aoki, Y., Kameyama, T., Saito, T., Masuda, S., Tanihata, J., Nagata, T., Mayeda, A., Takeda, SI., & Tsukahara, T. (2016). Endogenous multiple exon skipping and back-splicing at the DMD mutation hotspot. International journal of molecular sciences, 17(10), [1722]. https://doi.org/10.3390/ijms17101722