The domain encoded by exon 2 of the survival motor neuron protein mediates nucleic acid binding

Hum Mol Genet. 1998 Aug;7(8):1269-75. doi: 10.1093/hmg/7.8.1269.


Spinal muscular atrophy (SMA) is a motor neuron disorder resulting from anterior horn cell death. Survival motor neuron ( SMN ) is the SMA-determining gene and is deleted or gene converted in >95% of SMA patients. The SMN protein has a role in spliceosomal snRNP biogenesis and has therefore been implicated indirectly in general cellular RNA processing due to its unique sub-nuclear localization within structures termed 'gems', which co-localize with spliceosomal factors within coiled bodies. In this report, direct SMN RNA-binding activity, in addition to ssDNA and dsDNA binding is demonstrated. The region of SMN encoded by exon 2 is necessary and sufficient to mediate its nucleic acid-binding activities. This domain is homologous to several nucleic acid-binding factors, including several high mobility group (HMG) proteins. Additionally, previously reported SMN missense mutations isolated from SMA patients demonstrated reduced RNA-binding activity, suggesting that nucleic acid binding is functionally significant.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites / genetics
  • Cyclic AMP Response Element-Binding Protein
  • DNA / metabolism
  • Exons / genetics
  • Humans
  • Molecular Sequence Data
  • Muscular Atrophy, Spinal / genetics*
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism*
  • Protein Binding
  • RNA / metabolism
  • RNA-Binding Proteins
  • SMN Complex Proteins


  • Cyclic AMP Response Element-Binding Protein
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • SMN Complex Proteins
  • RNA
  • DNA