tailieunhanh - Báo cáo khoa học: 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-transcrip-tional control. For the latter case, inherent PAI-2 mRNA instability was previously shown to require a nonameric adenylate-uridylate element in the 3¢ UTR. | ỊFEBS Journal 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 Stan Stasinopoulos1 Mythily Mariasegaram1 Chris Gafforini1 Yoshikuni Nagamine2 and Robert L. Medcalf1 1 Monash University Australian Centre for Blood Diseases Melbourne Victoria Australia 2 Friedrich Miescher Institute for BiomedicalResearch Basel Switzerland Keywords 3 untranslated region adenylate and uridylate-rich element mRNA decay plasminogen activator inhibitor type 2 Correspondence R. Medcalf Australian Centre for Blood Diseases Monash University 6th Floor Burnet Building AMREP 89 Commercial Road Melbourne 3004 Australia Fax 61 3 9903 0228 Tel 61 3 9903 0133 E-mail Received 21 August 2009 revised 23 December 2009 accepted 28 December 2009 doi 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.