Spinal muscular atrophy: the role of SMN in axonal mRNA regulation

Brain Res. 2012 Jun 26;1462:81-92. doi: 10.1016/j.brainres.2012.01.044. Epub 2012 Jan 28.

Abstract

Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by homozygous mutations or deletions in the survival of motor neuron (SMN1) gene, encoding the ubiquitously expressed SMN protein. SMN associates with different proteins (Gemins 2-8, Unrip) to form a multimeric complex involved in the assembly of small nuclear ribonucleoprotein complexes (snRNPs). Since this activity is essential for the survival of all cell types, it still remains unclear why motor neurons are selectively vulnerable to low levels of SMN protein. Aside from its housekeeping role in the assembly of snRNPs, additional functions of SMN have been proposed. The well-documented localization of SMN in axonal transport granules and its interaction with numerous mRNA-binding proteins not involved in splicing regulation suggest a role in axonal RNA metabolism. This review will focus on the neuropathological and experimental evidence supporting a role for SMN in regulating the assembly, localization, or stability of axonal messenger ribonucleoprotein complexes (mRNPs). Furthermore, how defects in this non-canonical SMN function may contribute to the motor neuron pathology observed in SMA will be discussed. 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
  • Axons / physiology*
  • Cytoplasm / metabolism
  • Cytoskeleton / metabolism
  • Gene Expression Regulation
  • Humans
  • Muscular Atrophy, Spinal / genetics*
  • RNA, Messenger / genetics*
  • RNA-Binding Proteins / metabolism
  • SMN Complex Proteins / biosynthesis
  • SMN Complex Proteins / genetics*
  • Survival of Motor Neuron 1 Protein

Substances

  • RNA, Messenger
  • RNA-Binding Proteins
  • SMN Complex Proteins
  • Survival of Motor Neuron 1 Protein