Iron-mediated stability of PAI-1 mRNA in adenocarcinoma cells-involvement of a mRNA-binding nuclear protein.
This study reports the stability of mRNA of type-1 plasminogen activator inhibitor (PAI-1), the major physiologic inhibitor of plasminogen activation, by deferoxamine-aided iron deprivation, in PC3 adenocarcinoma cells. ELISA and Northern analyses studies revealed dose-dependent increase in PAI-1 expression by deferoxamine-treated cells. Co-treatment with ferric citrate quenched the effect of deferoxamine, confirming the role of iron in PAI-1 regulation. DRB-based RNA chase experiments suggested that post-transcriptional mechanism was involved in PAI-1 regulation. De-novo protein synthesis was necessary for this regulation. Electrophoretic mobility shift assay revealed the presence of a nuclear protein, binding to the 3'-UTR of PAI-1 mRNA in an iron-mediated manner. This is the first report of iron-mediated mRNA-protein interaction in PAI-1, involved in mRNA stability.
Radha
K S
KS
Department of Physiology, Miyazaki Medical College, Kihara 5200, Kiyotake-cho, Miyazaki 889-1692, Japan. radharao@med.miyazaki-u.ac.jp
Sugiki
Masahiko
M
Yoshida
Etsuo
E
Harish Kumar
M
M
Omura
Sayuri
S
Maruyama
Masugi
M
D020413:3' Untranslated Regions; D000230:Adenocarcinoma / Q000473:pathology*; D045744:Cell Line, Tumor; D003676:Deferoxamine / Q000494:pharmacology; D005290:Ferric Compounds / Q000494:pharmacology; D006801:Humans; D007501:Iron / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000494:pharmacology; D009687:Nuclear Proteins / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D020871:RNA Stability / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*
D020413:3' Untranslated Regions; D005290:Ferric Compounds; D007502:Iron Chelating Agents; D009687:Nuclear Proteins; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C025314:ferric citrate; D007501:Iron; D003676:Deferoxamine