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Prepublished online as a Blood First Edition Paper on April 17, 2002; DOI 10.1182/blood-2002-02-0412.
Submitted February 8, 2002
Accepted March 4, 2002
The G20210A Mutation Does Not Affect the Stability of Prothrombin mRNA in vivo
Eleanor S Pollak, Ho-Sun Lam, and J. E Russell*
Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; The Children's Hospital of Philadelphia, Philadelphia, PA, USA
Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA; The Children's Hospital of Philadelphia, Philadelphia, PA, USA
* Corresponding author; email: jeruss{at}mail.med.upenn.edu.
The activated form of prothrombin plays pivotal roles in the regulation of crucial coagulation, fibrinolytic, and cellular processes. Among several congenital genetic defects affecting the prothrombin gene, a G->A mutation at position 20210--the accepted polyadenylation site--has been linked to hyperprothrombinemia and a corresponding increase in venous and arterial thrombotic risk. The current study substantiates the hypothesis that the 20210A mutation effects post-transcriptional dysregulation of the prothrombin mRNA. Moreover, data from experiments carried out in fresh liver tissue indicate that the 20210A mutation does not affect prothrombin mRNA stability, but rather effects a change in the location of the 3' cleavage/polyadenylation reaction. Based upon this evidence, we propose an alternate model for the dysregulated expression of the prothrombin 20210A gene that does not require a change in the stability of its mRNA.
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