Missense mutation clustering in the survival motor neuron gene: a role for a conserved tyrosine and glycine rich region of the protein in RNA metabolism?

Hum Mol Genet. 1997 Mar;6(3):497-500. doi: 10.1093/hmg/6.3.497.

Abstract

The Survival Motor Neuron (SMN) gene shows deletions in the majority of patients with Spinal Muscular Atrophy (SMA), a disease of motor neuron degeneration. To date only two missense mutations have been reported in SMN in patients with SMA. The fact that no SMN-homologues have been forthcoming from data-base searching has resulted in a lack of hypotheses concerning the structural and functional consequences of these mutations. Recently SMN has been shown to interact with heterogeneous nuclear ribonucleoproteins (hnRNPs) suggesting a role in mRNA metabolism. We describe a novel missense mutation and the subsequent identification of a triplicated tyrosine-glycine (Y-G) peptide sequence at the C-terminal of SMN which encompasses each of the three predicted amino acid sequence substitutions. We have identified apparent orthologues of SMN in Caenorhabditis elegans and Schizosaccharomyces pombe. These sequences retain the highly conserved Y-G motif and provide additional support for a role of SMN in mRNA metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / chemistry
  • Cloning, Molecular
  • Conserved Sequence / genetics
  • Cyclic AMP Response Element-Binding Protein
  • Female
  • Glycine / chemistry
  • Humans
  • Male
  • Mice
  • Molecular Sequence Data
  • Muscular Atrophy, Spinal / genetics*
  • Mutation*
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics*
  • Pedigree
  • Polymorphism, Single-Stranded Conformational
  • RNA / metabolism*
  • RNA-Binding Proteins
  • SMN Complex Proteins
  • Saccharomyces / chemistry
  • Sequence Alignment
  • Sequence Analysis
  • Tyrosine / chemistry

Substances

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