Prothrombin G20210A is a bifunctional gene polymorphism

Détails

ID Serval
serval:BIB_827EC0426C68
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Prothrombin G20210A is a bifunctional gene polymorphism
Périodique
Thrombosis and Haemostasis
Auteur⸱e⸱s
Carter  A. M., Sachchithananthan  M., Stasinopoulos  S., Maurer  F., Medcalf  R. L.
ISSN
0340-6245 (Print)
Statut éditorial
Publié
Date de publication
05/2002
Volume
87
Numéro
5
Pages
846-53
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: May
Résumé
The G20210A polymorphism has been shown to alter the efficiency of prothrombin mRNA processing. Here we show that the G20210A mutation also alters prothrombin mRNA stability. Three-fold more prothrombin protein and mRNA were produced in NIH-3T3 cells transfected with the prothrombin cDNAs containing the 20210A variant compared to cells expressing the 20210G variant. mRNA stability assays using chimeric globin transcripts harboring the G or A variant of the 97 nt prothrombin 3'-UTR indicated that the 20210G variant conferred greater instability to the globin reporter transcript than the A variant in transfected HepG2 cells. Both variants of the prothrombin 3'-UTR were shown to provide binding sites for a number of cellular proteins including HuR, an RNA binding protein associated with mRNA stability. Our results indicate that the G20210A is a bifunctional polymorphism, as it not only alters the efficiency of mRNA processing, but also the decay rate of prothrombin mRNA.
Mots-clé
3' Untranslated Regions/*genetics 3T3 Cells Alleles Animals *Antigens, Surface Binding Sites DNA, Complementary/genetics DNA, Recombinant/genetics Electrophoretic Mobility Shift Assay Gene Expression Regulation Genes, Reporter Globins/genetics *Heterogeneous-Nuclear Ribonucleoprotein D Humans Mice *Polymorphism, Genetic Protein Biosynthesis Prothrombin/biosynthesis/*genetics RNA, Messenger/genetics/*metabolism RNA-Binding Proteins/metabolism Regulatory Sequences, Nucleic Acid Transcription, Genetic Transfection Tumor Cells, Cultured
Pubmed
Web of science
Création de la notice
25/01/2008 14:19
Dernière modification de la notice
20/08/2019 14:42
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