Unique preservation of neural cells in Hutchinson- Gilford progeria syndrome is due to the expression of the neural-specific miR-9 microRNA

Cell Rep. 2012 Jul 26;2(1):1-9. doi: 10.1016/j.celrep.2012.05.015. Epub 2012 Jun 21.


One puzzling observation in patients affected with Hutchinson-Gilford progeria syndrome (HGPS), who overall exhibit systemic and dramatic premature aging, is the absence of any conspicuous cognitive impairment. Recent studies based on induced pluripotent stem cells derived from HGPS patient cells have revealed a lack of expression in neural derivatives of lamin A, a major isoform of LMNA that is initially produced as a precursor called prelamin A. In HGPS, defective maturation of a mutated prelamin A induces the accumulation of toxic progerin in patient cells. Here, we show that a microRNA, miR-9, negatively controls lamin A and progerin expression in neural cells. This may bear major functional correlates, as alleviation of nuclear blebbing is observed in nonneural cells after miR-9 overexpression. Our results support the hypothesis, recently proposed from analyses in mice, that protection of neural cells from progerin accumulation in HGPS is due to the physiologically restricted expression of miR-9 to that cell lineage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival / genetics
  • Cells, Cultured
  • Gene Expression / physiology
  • Humans
  • Lamin Type A
  • Laminin / genetics
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • MicroRNAs / physiology*
  • Models, Biological
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / pathology
  • Neural Stem Cells / physiology
  • Neurons / metabolism
  • Neurons / pathology*
  • Neurons / physiology*
  • Nuclear Proteins / genetics
  • Organ Specificity / genetics
  • Progeria / genetics
  • Progeria / metabolism
  • Progeria / pathology*
  • Protein Precursors / genetics


  • Lamin Type A
  • Laminin
  • MIRN92 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • Protein Precursors
  • prelamin A
  • laminin A