The plasminogen activator inhibitor 2 transcript is destabilized via a multi-component 3' UTR localized adenylate and uridylate-rich instability element in an analogous manner to cytokines and oncogenes.
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.
Stasinopoulos
Stan
S
Monash University, Australian Centre for Blood Diseases, Melbourne, Victoria, Australia.
Mariasegaram
Mythily
M
Gafforini
Chris
C
Nagamine
Yoshikuni
Y
Medcalf
Robert L
RL
D020413:3' Untranslated Regions / Q000502:physiology; D000818:Animals; D001483:Base Sequence; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009857:Oncogenes / Q000235:genetics*; D017396:Plasminogen Activator Inhibitor 2 / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats
D020413:3' Untranslated Regions; D016207:Cytokines; D017396:Plasminogen Activator Inhibitor 2; D012333:RNA, Messenger