Post-transcriptional regulation of expression of plasminogen activator inhibitor type 1 mRNA by insulin and insulin-like growth factor 1.
In humans and non-human primates, alternative cleavage and polyadenylation of plasminogen activator inhibitor type-1 (PAI-1) pre-mRNA transcripts results in two forms of mature mRNA, an unstable 3.2-kilobase (kb) form, and a relatively more stable 2.2-kb form. Insulin and insulin-like growth factor I (IGF-1) increase steady state levels of PAI-1 mRNA in Hep G2 cells independently and synergistically. In the present study we found that the rate of transcription of the PAI-1 gene is not affected by insulin, IGF-1, or both but that insulin prolongs the half-life of the 3.2-kb PAI-1 mRNA species 2.7-fold without affecting the half-life of the 2.2-kb species. In contrast IGF-1, alone or with insulin, markedly prolongs the half-lives of both species. Our results demonstrate a novel mechanism of regulation of expression of the PAI-1 gene by insulin and IGF-1 operating at the post-transcriptional level.
Fattal
P G
PG
Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri 63110.
Schneider
D J
DJ
Sobel
B E
BE
Billadello
J J
JJ
D000818:Animals; D015152:Blotting, Northern; D003513:Cycloheximide / Q000494:pharmacology; D005786:Gene Expression Regulation; D006207:Half-Life; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D015849:Plasminogen Inactivators / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D007328:Insulin; D015849:Plasminogen Inactivators; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D003513:Cycloheximide