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

Stasinopoulos, Stan, Mariasegaram, Mythily, Gafforini, Chris, Nagamine, Yoshikuni and Medcalf, Robert L. (2010) 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. The Federation of European Biochemical Societies (FEBS) Journal, 277 5: 1331-1344. doi:10.1111/j.1742-4658.2010.07563.x


Author Stasinopoulos, Stan
Mariasegaram, Mythily
Gafforini, Chris
Nagamine, Yoshikuni
Medcalf, Robert L.
Title 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
Journal name The Federation of European Biochemical Societies (FEBS) Journal   Check publisher's open access policy
ISSN 1742-464X
1742-4658
Publication date 2010-03
Sub-type Article (original research)
DOI 10.1111/j.1742-4658.2010.07563.x
Volume 277
Issue 5
Start page 1331
End page 1344
Total pages 14
Place of publication Oxford, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Formatted abstract
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.
Keyword 3′ Untranslated region
Adenylate and uridylate-rich element
mRNA decay
Plasminogen activator inhibitor type 2
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
ERA 2012 Admin Only
 
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Created: Fri, 21 Oct 2011, 14:31:25 EST by Mythily Mariasegaram on behalf of UQ Centre for Clinical Research