Post-transcriptional regulation of expression of plasminogen activator inhibitor type 1 mRNA by insulin and insulin-like growth factor 1

Abstract

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.