SRp30c-dependent stimulation of survival motor neuron (SMN) exon 7 inclusion is facilitated by a direct interaction with hTra2β1

Philip J. Young, Christine J. DiDonato, Diane Hu, Rashmi Kothary, Elliot Androphy, Christian L. Lorson

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

Proximal spinal muscular atrophy (SMA) is caused by the homozygous loss of survival motor neuron (SMN1). SMN2, a nearly identical copy gene, is present in all SMA patients; however this gene cannot provide protection from disease-due to the aberrant splicing of a critical exon. SMN1-derived transcripts are exclusively full-length, whereas SMN2-derived transcripts predominantly lack SMN exon 7. A single non-polymorphic nucleotide difference (C in SMN1; T in SMN2) is responsible for the alternative splicing patterns. We have previously shown that transient expression of an SR-like splicing factor, hTra2β1, stimulates inclusion of exon 7 in SMN2-derived mini-gene transcripts through an interaction with the AG-rich exonic splice enhancer within exon 7. We now demonstrate that a second splicing factor, SRp30c, can stimulate SMN exon 7-inclusion and that this activity required the same AG-rich enhancer as hTra2β1. SRp30c did not directly associate with SMN exon 7; rather its association with the exonic enhancer was mediated by a direct interaction with hTra2β1. In the absence of the hTra2β1 binding site, SRp30c failed to complex with SMN exon 7. Taken together, these results identify SRp30c as a modulator of SMN exon 7-inclusion and provide insight into the molecular regulation of this critical exon.

Original languageEnglish (US)
Pages (from-to)577-587
Number of pages11
JournalHuman Molecular Genetics
Volume11
Issue number5
StatePublished - Mar 1 2002
Externally publishedYes

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Motor Neurons
Exons
Spinal Muscular Atrophy
SMN Complex Proteins
Genes
Alternative Splicing
Nucleotides
Binding Sites

ASJC Scopus subject areas

  • Genetics

Cite this

SRp30c-dependent stimulation of survival motor neuron (SMN) exon 7 inclusion is facilitated by a direct interaction with hTra2β1. / Young, Philip J.; DiDonato, Christine J.; Hu, Diane; Kothary, Rashmi; Androphy, Elliot; Lorson, Christian L.

In: Human Molecular Genetics, Vol. 11, No. 5, 01.03.2002, p. 577-587.

Research output: Contribution to journalArticle

Young, Philip J. ; DiDonato, Christine J. ; Hu, Diane ; Kothary, Rashmi ; Androphy, Elliot ; Lorson, Christian L. / SRp30c-dependent stimulation of survival motor neuron (SMN) exon 7 inclusion is facilitated by a direct interaction with hTra2β1. In: Human Molecular Genetics. 2002 ; Vol. 11, No. 5. pp. 577-587.
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