Normal and Altered Pre-mRNA Processing in the DMD Gene

Overview

Journal Hum Genet

Specialty Genetics

Date 2017 Jun 10

PMID 28597072

Citations 28

Authors

Sylvie Tuffery-Giraud

Julie Miro

Michel Koenig

Mireille Claustres

Affiliations

Soon will be listed here.

Abstract

Splicing of pre-mRNA is a crucial regulatory stage in the pathway of gene expression controlled by multiple post- and co-transcriptional mechanisms. The large Duchenne muscular dystrophy gene encoding the protein dystrophin provides a striking example of the complexity of human pre-mRNAs. In this review, we summarize the current state of knowledge about canonical and non-canonical splicing in the DMD pre-mRNA, with a focus on mechanisms that take place in the full-length transcript isoform expressed in human skeletal muscle. In particular, we highlight recent work demonstrating that multi-step events are required for long DMD intron removal. The role of temporary intron retention in the occurrence of alternative splicing events is also discussed. Even though the proportion of splicing mutations is lower than reported in other genes, a great diversity of splicing defects linked to point mutations, but also large genomic rearrangements are observed in the DMD gene. We provide an overview of the molecular mechanisms underlying aberrant splicing in patients with Duchenne or Becker muscular dystrophy, and we also detail how alternative splicing can serve as a disease modifier in patients by changing the outcome of the primary defect.

Citing Articles

Deletion of exons 45 to 55 in the DMD gene: from the therapeutic perspective to the in vitro model.

Poyatos-Garcia J, Soblechero-Martin P, Liquori A, Lopez-Martinez A, Maestre P, Gonzalez-Romero E Skelet Muscle. 2024; 14(1):21.

PMID: 39354597 PMC: 11443720. DOI: 10.1186/s13395-024-00353-3.

Splice modulation strategy applied to deep intronic variants in causing recessive dystrophic epidermolysis bullosa.

Pironon N, Bourrat E, Prost C, Chen M, Woodley D, Titeux M Proc Natl Acad Sci U S A. 2024; 121(35):e2401781121.

PMID: 39159368 PMC: 11363305. DOI: 10.1073/pnas.2401781121.

A novel deep intronic variant introduce pseudoexon in Becker muscular dystrophy: A case report.

Liu C, Lu Y, Yu H, Xie Z, Sun C, Cheng X Heliyon. 2024; 10(6):e28020.

PMID: 38545205 PMC: 10966583. DOI: 10.1016/j.heliyon.2024.e28020.

Dystrophin- and Utrophin-Based Therapeutic Approaches for Treatment of Duchenne Muscular Dystrophy: A Comparative Review.

Szwec S, Kaplucha Z, Chamberlain J, Konieczny P BioDrugs. 2023; 38(1):95-119.

PMID: 37917377 PMC: 10789850. DOI: 10.1007/s40259-023-00632-3.

SpliceAI-visual: a free online tool to improve SpliceAI splicing variant interpretation.

de Sainte Agathe J, Filser M, Isidor B, Besnard T, Gueguen P, Perrin A Hum Genomics. 2023; 17(1):7.

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