SMN control of RNP assembly: from post-transcriptional gene regulation to motor neuron disease

Semin Cell Dev Biol. 2014 Aug:32:22-9. doi: 10.1016/j.semcdb.2014.04.026. Epub 2014 Apr 24.

Abstract

At the post-transcriptional level, expression of protein-coding genes is controlled by a series of RNA regulatory events including nuclear processing of primary transcripts, transport of mature mRNAs to specific cellular compartments, translation and ultimately, turnover. These processes are orchestrated through the dynamic association of mRNAs with RNA binding proteins and ribonucleoprotein (RNP) complexes. Accurate formation of RNPs in vivo is fundamentally important to cellular development and function, and its impairment often leads to human disease. The survival motor neuron (SMN) protein is key to this biological paradigm: SMN is essential for the biogenesis of various RNPs that function in mRNA processing, and genetic mutations leading to SMN deficiency cause the neurodegenerative disease spinal muscular atrophy. Here we review the expanding role of SMN in the regulation of gene expression through its multiple functions in RNP assembly. We discuss advances in our understanding of SMN activity as a chaperone of RNPs and how disruption of SMN-dependent RNA pathways can cause motor neuron disease.

Keywords: RNA processing; Ribonucleoprotein complexes (RNPs); Sm and LSm proteins; Small nuclear RNA (snRNA); Spinal muscular atrophy (SMA); Survival motor neuron (SMN).

Publication types

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

MeSH terms

  • Animals
  • Gene Expression Regulation*
  • Humans
  • Models, Genetic
  • Motor Neuron Disease / genetics
  • Motor Neuron Disease / metabolism*
  • Motor Neurons / metabolism*
  • RNA Splicing
  • RNA Stability
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / metabolism*
  • SMN Complex Proteins / genetics
  • SMN Complex Proteins / metabolism*

Substances

  • Ribonucleoproteins
  • SMN Complex Proteins