Spliceosomal small nuclear ribonucleoprotein biogenesis defects and motor neuron selectivity in spinal muscular atrophy

Brain Res. 2012 Jun 26:1462:93-9. doi: 10.1016/j.brainres.2012.02.051. Epub 2012 Feb 28.

Abstract

The SMN protein is essential and participates in the assembly of macromolecular complexes of RNA and protein in all cells. The best-characterized function of SMN is as an assembler of spliceosomal small nuclear ribonucleoproteins (snRNPs). SMN performs this function as part of a complex with several other proteins called Gemins. snRNPs are assembled in the cytoplasm in a stepwise manner and then are imported to the nucleus where they participate globally in the splicing of pre-mRNA. Mutations in the SMN1 gene result in the motor neuron disease, spinal muscular atrophy (SMA). Most of these mutations result in a reduction in the expression levels of the SMN protein, which, in turn, results in a reduction in snRNP assembly capacity. This review highlights current studies that have investigated the mechanism of SMN-dependent snRNP assembly, as well as the downstream effects on pre-mRNA splicing that result from a decrease in SMN. This article is part of a Special Issue entitled "RNA-Binding Proteins".

Publication types

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

MeSH terms

  • Animals
  • Humans
  • Motor Neuron Disease / genetics*
  • Motor Neuron Disease / physiopathology
  • Motor Neurons / physiology*
  • Muscular Atrophy, Spinal / genetics*
  • Muscular Atrophy, Spinal / physiopathology
  • Mutation / genetics
  • Mutation / physiology
  • Ribonucleoproteins, Small Nuclear / biosynthesis*
  • Ribonucleoproteins, Small Nuclear / genetics
  • Survival of Motor Neuron 1 Protein / genetics
  • Survival of Motor Neuron 1 Protein / physiology

Substances

  • Ribonucleoproteins, Small Nuclear
  • SMN1 protein, human
  • Survival of Motor Neuron 1 Protein