Journal Article

An exonic enhancer is required for inclusion of an essential exon in the SMA-determining gene <i>SMN</i>

Christian L. Lorson and Elliot J. Androphy

in Human Molecular Genetics

Volume 9, issue 2, pages 259-265
Published in print January 2000 | ISSN: 0964-6906
Published online January 2000 | e-ISSN: 1460-2083 | DOI:
An exonic enhancer is required for inclusion of an essential exon in the SMA-determining gene SMN

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The survival motor neuron genes, SMN1 and SMN2, encode identical proteins; however, only homo‐ zygous loss of SMN1 correlates with the development of spinal muscular atrophy (SMA). We have previously shown that a single non-polymorphic nucleotide difference in SMN exon 7 dramatically affects SMN mRNA processing. SMN1 primarily produces a full-length RNA whereas SMN2 expresses dramatically reduced full-length RNA and abundant levels of an aberrantly spliced transcript lacking exon 7. The importance of proper exon 7 processing has been underscored by the identification of several mutations within splice sites adjacent to exon 7. Here we show that an AG-rich exonic splice enhancer (ESE) in the center of SMN exon 7 is required for inclusion of exon 7. This region functioned as an ESE in a heterologous context, supporting efficient in vitro splicing of the Drosophila double-sex gene. Finally, the protein encoded by the exon-skipping event, Δ7, was less stable than full-length SMN, providing additional evidence of why SMN2 fails to compensate for the loss of SMN1 and leads to the development of SMA.

Journal Article.  6227 words.  Illustrated.

Subjects: Genetics and Genomics

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