Prothrombin G20210A is a bifunctional gene polymorphism
Details
Serval ID
serval:BIB_827EC0426C68
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Prothrombin G20210A is a bifunctional gene polymorphism
Journal
Thrombosis and Haemostasis
ISSN
0340-6245 (Print)
Publication state
Published
Issued date
05/2002
Volume
87
Number
5
Pages
846-53
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: May
Research Support, Non-U.S. Gov't --- Old month value: May
Abstract
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.
Keywords
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
Create date
25/01/2008 15:19
Last modification date
20/08/2019 15:42