SMN deficiency reduces cellular ability to form stress granules, sensitizing cells to stress

Cell Mol Neurobiol. 2011 May;31(4):541-50. doi: 10.1007/s10571-011-9647-8. Epub 2011 Jan 15.


Spinal Muscular Atrophy (SMA) is a neurodegenerative disease that is caused by deletion of the SMN (Survival of Motor Neuron) gene. The SMN protein is essential for cell survival and co-localized with TIA-1/R and G3BP, two characteristic markers of stress granules (SGs). To further study the SMN function in stress granules and in response to stress, we generated stable cell lines with SMN knockdown. Our data indicate that suppression of SMN drastically reduces cellular ability to form stress granules in response to stress treatment. In addition, we show that SMN deficiency sensitizes cells to sodium arsenite and H(2)O(2), two well-known stress inducers, leading to cell death at a much lower concentration of inducers in SMN knockdown cells than in control cells. Interestingly, the cell death is correlated with formation of stress granules, suggesting that involvement of SMN in formation of stress granules may play an important role in cell survival. Furthermore, rescue of SGs formation by overexpression of G3BP can reverse the defective formation of stress granules and results in partial abrogation of cell death against SMN deficiency. We deduce that modulation of stress response may be useful for potential SMN treatment.

MeSH terms

  • Animals
  • Arsenites / pharmacology
  • Carrier Proteins / metabolism
  • Cell Death / drug effects
  • Cell Survival / drug effects
  • Cytoplasmic Granules / drug effects
  • Cytoplasmic Granules / metabolism*
  • Cytoprotection / drug effects
  • Down-Regulation / drug effects
  • Eukaryotic Initiation Factor-2 / metabolism
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Mice
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism
  • PC12 Cells
  • Phosphorylation / drug effects
  • RNA Interference / drug effects
  • RNA, Small Interfering / metabolism
  • Rats
  • Sodium Compounds / pharmacology
  • Stress, Physiological* / drug effects
  • Survival of Motor Neuron 1 Protein / metabolism*
  • Transfection


  • Arsenites
  • Carrier Proteins
  • Eukaryotic Initiation Factor-2
  • RNA, Small Interfering
  • Sodium Compounds
  • Survival of Motor Neuron 1 Protein
  • sodium arsenite
  • Hydrogen Peroxide