title: Unique preservation of neural cells in Hutchinson- Gilford progeria syndrome is due to the expression of the neural-specific miR-9 microRNA.
abstract: 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.
authors: CECS, I-STEM, AFM, Institute for Stem Cell Therapy and Exploration of Monogenic Diseases, 5 rue Henri Desbruères, 91030 Evry cedex, France. xnissan@istem.fr
authors: Xavier
authors: X
authors: Nissan
authors: Sophie
authors: S
authors: Blondel
authors: Claire
authors: C
authors: Navarro
authors: Yves
authors: Y
authors: Maury
authors: Cécile
authors: C
authors: Denis
authors: Mathilde
authors: M
authors: Girard
authors: Cécile
authors: C
authors: Martinat
authors: Annachiara
authors: A
authors: De Sandre-Giovannoli
authors: Nicolas
authors: N
authors: Levy
authors: Marc
authors: M
authors: Peschanski
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D034904:Lamin Type A; D007797:Laminin / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D058953:Neural Stem Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000473:pathology* / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics; D009928:Organ Specificity / Q000235:genetics; D011371:Progeria / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011498:Protein Precursors / Q000235:genetics
chemical_list: D034904:Lamin Type A; D007797:Laminin; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D011498:Protein Precursors; C090764:prelamin A; C084098:laminin A