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PubMed · 12038788

Prothrombin G20210A is a bifunctional gene polymorphism.

Angela M Carter·Mythily Sachchithananthan·Stan Stasinopoulos·Fabienne Maurer·Robert L Medcalf
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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.

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3' Untranslated Regions3T3 CellsAllelesAnimalsAntigens, SurfaceBinding SitesDNA, ComplementaryDNA, RecombinantELAV ProteinsELAV-Like Protein 1Electrophoretic Mobility Shift AssayGene Expression RegulationGenes, ReporterGlobinsHeterogeneous Nuclear Ribonucleoprotein D0Heterogeneous-Nuclear Ribonucleoprotein DHumansMicePolymorphism, GeneticProtein BiosynthesisProthrombinRNA, MessengerRNA-Binding ProteinsRegulatory Sequences, Nucleic AcidTranscription, GeneticTransfectionTumor Cells, CulturedJournal ArticleResearch Support, Non-U.S. Gov't

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Angela M Carter, Mythily Sachchithananthan, Stan Stasinopoulos, Fabienne Maurer, Robert L Medcalf. 2002. Prothrombin G20210A is a bifunctional gene polymorphism.. https://pubmed.ncbi.nlm.nih.gov/12038788/

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