Plasminogen activator inhibitor type 2 (PAI‐2; SERPINB2) is a highly‐regulated gene that is subject to both transcriptional and post‐transcriptional control. For the latter case, inherent PAI‐2 mRNA instability was previously shown to require a nonameric adenylate‐uridylate element in the 3′ UTR. However, mutation of this site was only partially effective at restoring complete mRNA stabilization. In the present study, we have identified additional regulatory motifs within the 3′ UTR that cooperate with the nonameric adenylate‐uridylate element to promote mRNA destabilization. These elements are located within a 74 nucleotide U‐rich stretch (58%) of the 3′ UTR that flanks the nonameric motif; deletion or substitution of this entire region results in complete mRNA stabilization. These new elements are conserved between species and optimize the destabilizing capacity with the nonameric element to ensure complete mRNA instability in a manner analogous to some class I and II adenylate‐uridylate elements present in transcripts encoding oncogenes and cytokines. Hence, post‐transcriptional regulation of the PAI‐2 mRNA transcript involves an interaction between closely spaced adenylate‐uridylate elements in a manner analogous to the post‐transcriptional regulation of oncogenes and cytokines.