Prothrombin G20210A is a bifunctional gene polymorphism.
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.
Carter
Angela M
AM
Academic Unit of Molecular Vascular Medicine, University of Leeds, United Kingdom.
Sachchithananthan
Mythily
M
Stasinopoulos
Stan
S
Maurer
Fabienne
F
Medcalf
Robert L
RL
D020413:3' Untranslated Regions / Q000235:genetics*; D016475:3T3 Cells; D000483:Alleles; D000818:Animals; D000954:Antigens, Surface; D001665:Binding Sites; D018076:DNA, Complementary / Q000235:genetics; D004274:DNA, Recombinant / Q000235:genetics; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D005914:Globins / Q000235:genetics; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D006801:Humans; D051379:Mice; D011110:Polymorphism, Genetic; D014176:Protein Biosynthesis; D011516:Prothrombin / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D020413:3' Untranslated Regions; D000954:Antigens, Surface; D018076:DNA, Complementary; D004274:DNA, Recombinant; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; C000630987:Hnrpd protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011516:Prothrombin; D005914:Globins