SRp30c-dependent stimulation of survival motor neuron (SMN) exon 7 inclusion is facilitated by a direct interaction with hTra2 beta 1

Hum Mol Genet. 2002 Mar 1;11(5):577-87. doi: 10.1093/hmg/11.5.577.


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, hTra2 beta 1, 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 hTra2 beta 1. SRp30c did not directly associate with SMN exon 7; rather its association with the exonic enhancer was mediated by a direct interaction with hTra2 beta 1. In the absence of the hTra2 beta 1 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing
  • Base Sequence
  • Binding Sites
  • Cyclic AMP Response Element-Binding Protein
  • Enhancer Elements, Genetic / genetics
  • Exons
  • HeLa Cells
  • Humans
  • Motor Neurons / metabolism*
  • Muscular Atrophy, Spinal / genetics*
  • Muscular Atrophy, Spinal / metabolism
  • Nerve Tissue Proteins / genetics*
  • Nuclear Proteins / genetics*
  • Phosphoproteins / genetics*
  • Protein Isoforms / genetics
  • RNA / metabolism
  • RNA-Binding Proteins*
  • Recombinant Proteins / isolation & purification
  • SMN Complex Proteins
  • Serine-Arginine Splicing Factors
  • Survival of Motor Neuron 1 Protein
  • Survival of Motor Neuron 2 Protein
  • Transcription, Genetic
  • Tumor Cells, Cultured


  • Cyclic AMP Response Element-Binding Protein
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Phosphoproteins
  • Protein Isoforms
  • RNA-Binding Proteins
  • Recombinant Proteins
  • SMN Complex Proteins
  • SMN1 protein, human
  • SMN2 protein, human
  • Survival of Motor Neuron 1 Protein
  • Survival of Motor Neuron 2 Protein
  • TRA2B protein, human
  • Serine-Arginine Splicing Factors
  • RNA