A Drosophila model of spinal muscular atrophy uncouples snRNP biogenesis functions of survival motor neuron from locomotion and viability defects

Cell Rep. 2012 Jun 28;1(6):624-31. doi: 10.1016/j.celrep.2012.05.014. Epub 2012 Jun 21.


The spinal muscular atrophy (SMA) protein, survival motor neuron (SMN), functions in the biogenesis of small nuclear ribonucleoproteins (snRNPs). SMN has also been implicated in tissue-specific functions; however, it remains unclear which of these is important for the etiology of SMA. Smn null mutants display larval lethality and show significant locomotion defects as well as reductions in minor-class spliceosomal snRNAs. Despite these reductions, we found no appreciable defects in the splicing of mRNAs containing minor-class introns. Transgenic expression of low levels of either wild-type or an SMA patient-derived form of SMN rescued the larval lethality and locomotor defects; however, snRNA levels were not restored. Thus, the snRNP biogenesis function of SMN is not a major contributor to the phenotype of Smn null mutants. These findings have major implications for SMA etiology because they show that SMN's role in snRNP biogenesis can be uncoupled from the organismal viability and locomotor defects.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Cell Survival
  • Disease Models, Animal
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / deficiency
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / metabolism*
  • Humans
  • Introns / genetics
  • Larva
  • Locomotion*
  • Molecular Sequence Data
  • Muscular Atrophy, Spinal / pathology*
  • Muscular Atrophy, Spinal / physiopathology*
  • Mutation / genetics
  • Protein Structure, Quaternary
  • RNA Splicing / genetics
  • RNA, Small Nuclear / chemistry
  • RNA, Small Nuclear / genetics
  • RNA, Small Nuclear / metabolism
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Ribonucleoproteins, Small Nuclear / biosynthesis*
  • Ribonucleoproteins, Small Nuclear / metabolism


  • Drosophila Proteins
  • RNA, Small Nuclear
  • RNA-Binding Proteins
  • Ribonucleoproteins, Small Nuclear
  • Smn protein, Drosophila