miR-543 and miR-590-3p regulate human mesenchymal stem cell aging via direct targeting of AIMP3/p18

Age (Dordr). 2014;36(6):9724. doi: 10.1007/s11357-014-9724-2. Epub 2014 Dec 4.


Previously, AIMP3 (aminoacyl-tRNAsynthetase-interacting multifunctional protein-3) was shown to be involved in the macromolecular tRNA synthetase complex or to act as a tumor suppressor. In this study, we report a novel role of AIMP3/p18 in the cellular aging of human mesenchymal stem cells (hMSCs). We found that AIMP3/p18 expression significantly increased in senescent hMSCs and in aged mouse bone marrow-derived MSCs (mBM-MSCs). AIMP3/p18 overexpression is sufficient to induce the cellular senescence phenotypes with compromised clonogenicity and adipogenic differentiation potential. To identify the upstream regulators of AIMP3/p18 during senescence, we screened for potential epigenetic regulators and for miRNAs. We found that the levels of miR-543 and miR-590-3p significantly decreased under senescence-inducing conditions, whereas the AIMP3/p18 protein levels increased. We demonstrate for the first time that miR-543 and miR-590-3p are able to decrease AIMP3/p18 expression levels through direct binding to the AIMP/p18 transcripts, which further compromised the induction of the senescence phenotype. Taken together, our data demonstrate that AIMP3/p18 regulates cellular aging in hMSCs possibly through miR-543 and miR-590-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics*
  • Animals
  • Cells, Cultured
  • Cellular Senescence / drug effects
  • Cellular Senescence / genetics*
  • Gene Expression Regulation*
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Transgenic
  • MicroRNAs / genetics*
  • Mitomycin / pharmacology
  • Peptide Elongation Factors / genetics*
  • Protein Binding / genetics
  • Real-Time Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Transfection
  • Tumor Suppressor Proteins / genetics*


  • EEF1E1 protein, human
  • MIRN543 microRNA, human
  • MicroRNAs
  • Peptide Elongation Factors
  • Tumor Suppressor Proteins
  • Mitomycin