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

Christian L. Lorson, Elliot J. Androphy

Research output: Contribution to journalArticle

333 Scopus citations

Abstract

The survival motor neuron genes, SMN1 and SMN2, encode identical proteins; however, only homozygous 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, supportng 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.

Original languageEnglish (US)
Pages (from-to)259-266
Number of pages8
JournalHuman molecular genetics
Volume9
Issue number2
StatePublished - Jan 29 2000
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'An exonic enhancer is required for inclusion of an essential exon in the SMA-determining gene SMN'. Together they form a unique fingerprint.

  • Cite this