SMN in spinal muscular atrophy and snRNP biogenesis

Wiley Interdiscip Rev RNA. Jul-Aug 2011;2(4):546-64. doi: 10.1002/wrna.76. Epub 2011 Feb 17.

Abstract

Ribonucleoprotein (RNP) complexes function in nearly every facet of cellular activity. The spliceosome is an essential RNP that accurately identifies introns and catalytically removes the intervening sequences, providing exquisite control of spatial, temporal, and developmental gene expressions. U-snRNPs are the building blocks for the spliceosome. A significant amount of insight into the molecular assembly of these essential particles has recently come from a seemingly unexpected area of research: neurodegeneration. Survival motor neuron (SMN) performs an essential role in the maturation of snRNPs, while the homozygous loss of SMN1 results in the development of spinal muscular atrophy (SMA), a devastating neurodegenerative disease. In this review, the function of SMN is examined within the context of snRNP biogenesis and evidence is examined which suggests that the SMN functional defects in snRNP biogenesis may account for the motor neuron pathology observed in SMA.

Publication types

  • Review

MeSH terms

  • Alternative Splicing
  • Axons / metabolism
  • Humans
  • Models, Neurological
  • Muscular Atrophy, Spinal / classification
  • Muscular Atrophy, Spinal / etiology
  • Muscular Atrophy, Spinal / genetics*
  • Muscular Atrophy, Spinal / metabolism*
  • Protein Structure, Tertiary
  • RNA Precursors / genetics
  • RNA Precursors / metabolism
  • RNA Splicing
  • Ribonucleoproteins, Small Nuclear / biosynthesis*
  • Survival of Motor Neuron 1 Protein / chemistry
  • Survival of Motor Neuron 1 Protein / genetics*
  • Survival of Motor Neuron 1 Protein / metabolism*
  • Survival of Motor Neuron 2 Protein / genetics
  • Survival of Motor Neuron 2 Protein / metabolism

Substances

  • RNA Precursors
  • Ribonucleoproteins, Small Nuclear
  • SMN1 protein, human
  • SMN2 protein, human
  • Survival of Motor Neuron 1 Protein
  • Survival of Motor Neuron 2 Protein