RT Journal Article
SR Electronic
T1 Human antigen R binding and regulation of SOX2 mRNA in human mesenchymal stem cells
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP mol.115.100701
DO 10.1124/mol.115.100701
A1 Stephana Carelli
A1 Elisa Latorre
A1 Filippo Caremoli
A1 Toniella Giallongo
A1 Mattia Colli
A1 Alessandra Canazza
A1 Alessandro Provenzani
A1 Anna Maria Di Giulio
A1 Alfredo Gorio
YR 2015
UL http://molpharm.aspetjournals.org/content/early/2015/12/16/mol.115.100701.abstract
AB Since 2005, SOX2 has raised the attention of the scientific community for being one of the key transcription factors responsible for pluripotency induction in somatic stem cells. Our research investigated the turnover regulation of SOX2 mRNA in human adipose-derived stem cells, considered one of the most valuable sources of somatic stem cells in regenerative medicine. Mitoxantrone, is a drug acting on nucleic acids primarily used to treat certain types of cancer, and recently re-addressed to ameliorate the outcome of autoimmune diseases such as multiple sclerosis. Additionally, mitoxantrone has been shown to inhibit the binding of Human antigen R (HuR) RNA binding protein to TNF alpha mRNA. Our results show that HuR binds to the 3'UTR region of SOX2 mRNA together with the RNA-induced silencing complex-miR145. The HuR binding works by stabilizing the interaction between the 3' UTR and RISC. Cell exposure to mitoxantrone leads to HuR detachment, and the subsequent prolongation of the SOX2 mRNA half-life. The prolonged SOX2 half-life allows to an improvement of the spheroid forming capability of the adipose-derived stem cells. The silencing of HuR confirmed the above observations, and illustrates how the RNA binding protein HuR may be a required molecule for regulation of SOX2 mRNA decay.