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In-vivo analysis of splicing behaviour in XLDC

Alternative splicing of pre-mRNA is a versatile regulatory mechanism that significantly expands the range of possible end products from a single gene. We previously identified an intronic rearrangement in dystrophin intron 11 in one family with X-linked dilated cardiomyopathy (XLDC), causing incorporation of an aberrant exon in a tissue-specific manner.

In the present study we performed an in vivo splicing assay by using mini-genes containing part of the patient genomic rearrangement in C2C12 (skeletal muscle) myoblasts and myotubes, H9C2 (cardiac muscle) myocytes, and Hela cells.

We show that inclusion of the aberrant exon is favored in H9C2 and differentiated C2C12 myotubes. These data suggest that the aberrant exon undergoes a differentiation-specific splicing. Unexpectedly, length of intron has a significant influence upon alternative splicing with longer introns favouring the inclusion of the aberrant exon in the cardiac cells. These data suggest that cardiac cells are more prone to steric hindrance between trans-acting factors, involved in the inclusion of the Alu exon.

Reported by

Imperial College London
Imperial College
W12 ONN London
United Kingdom
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