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Signal-dependent splicing of tissue factor pre-mRNA modulates the thrombogenecity of human platelets

Tissue factor (TF) is an essential cofactor for the activation of blood coagulation in vivo. We now report that quiescent human platelets express TF pre-mRNA and, in response to activation, splice this intronic-rich message into mature mRNA. Splicing of TF pre-mRNA is associated with increased TF pr...

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Autores principales: Schwertz, Hansjörg, Tolley, Neal D., Foulks, Jason M., Denis, Melvin M., Risenmay, Ben W., Buerke, Michael, Tilley, Rachel E., Rondina, Matthew T., Harris, Estelle M., Kraiss, Larry W., Mackman, Nigel, Zimmerman, Guy A., Weyrich, Andrew S.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118136/
https://www.ncbi.nlm.nih.gov/pubmed/17060476
http://dx.doi.org/10.1084/jem.20061302
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author Schwertz, Hansjörg
Tolley, Neal D.
Foulks, Jason M.
Denis, Melvin M.
Risenmay, Ben W.
Buerke, Michael
Tilley, Rachel E.
Rondina, Matthew T.
Harris, Estelle M.
Kraiss, Larry W.
Mackman, Nigel
Zimmerman, Guy A.
Weyrich, Andrew S.
author_facet Schwertz, Hansjörg
Tolley, Neal D.
Foulks, Jason M.
Denis, Melvin M.
Risenmay, Ben W.
Buerke, Michael
Tilley, Rachel E.
Rondina, Matthew T.
Harris, Estelle M.
Kraiss, Larry W.
Mackman, Nigel
Zimmerman, Guy A.
Weyrich, Andrew S.
author_sort Schwertz, Hansjörg
collection PubMed
description Tissue factor (TF) is an essential cofactor for the activation of blood coagulation in vivo. We now report that quiescent human platelets express TF pre-mRNA and, in response to activation, splice this intronic-rich message into mature mRNA. Splicing of TF pre-mRNA is associated with increased TF protein expression, procoagulant activity, and accelerated formation of clots. Pre-mRNA splicing is controlled by Cdc2-like kinase (Clk)1, and interruption of Clk1 signaling prevents TF from accumulating in activated platelets. Elevated intravascular TF has been reported in a variety of prothrombotic diseases, but there is debate as to whether anucleate platelets—the key cellular effector of thrombosis—express TF. Our studies demonstrate that human platelets use Clk1-dependent splicing pathways to generate TF protein in response to cellular activation. We propose that platelet-derived TF contributes to the propagation and stabilization of a thrombus.
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spelling pubmed-21181362007-12-13 Signal-dependent splicing of tissue factor pre-mRNA modulates the thrombogenecity of human platelets Schwertz, Hansjörg Tolley, Neal D. Foulks, Jason M. Denis, Melvin M. Risenmay, Ben W. Buerke, Michael Tilley, Rachel E. Rondina, Matthew T. Harris, Estelle M. Kraiss, Larry W. Mackman, Nigel Zimmerman, Guy A. Weyrich, Andrew S. J Exp Med Brief Definitive Reports Tissue factor (TF) is an essential cofactor for the activation of blood coagulation in vivo. We now report that quiescent human platelets express TF pre-mRNA and, in response to activation, splice this intronic-rich message into mature mRNA. Splicing of TF pre-mRNA is associated with increased TF protein expression, procoagulant activity, and accelerated formation of clots. Pre-mRNA splicing is controlled by Cdc2-like kinase (Clk)1, and interruption of Clk1 signaling prevents TF from accumulating in activated platelets. Elevated intravascular TF has been reported in a variety of prothrombotic diseases, but there is debate as to whether anucleate platelets—the key cellular effector of thrombosis—express TF. Our studies demonstrate that human platelets use Clk1-dependent splicing pathways to generate TF protein in response to cellular activation. We propose that platelet-derived TF contributes to the propagation and stabilization of a thrombus. The Rockefeller University Press 2006-10-30 /pmc/articles/PMC2118136/ /pubmed/17060476 http://dx.doi.org/10.1084/jem.20061302 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Brief Definitive Reports
Schwertz, Hansjörg
Tolley, Neal D.
Foulks, Jason M.
Denis, Melvin M.
Risenmay, Ben W.
Buerke, Michael
Tilley, Rachel E.
Rondina, Matthew T.
Harris, Estelle M.
Kraiss, Larry W.
Mackman, Nigel
Zimmerman, Guy A.
Weyrich, Andrew S.
Signal-dependent splicing of tissue factor pre-mRNA modulates the thrombogenecity of human platelets
title Signal-dependent splicing of tissue factor pre-mRNA modulates the thrombogenecity of human platelets
title_full Signal-dependent splicing of tissue factor pre-mRNA modulates the thrombogenecity of human platelets
title_fullStr Signal-dependent splicing of tissue factor pre-mRNA modulates the thrombogenecity of human platelets
title_full_unstemmed Signal-dependent splicing of tissue factor pre-mRNA modulates the thrombogenecity of human platelets
title_short Signal-dependent splicing of tissue factor pre-mRNA modulates the thrombogenecity of human platelets
title_sort signal-dependent splicing of tissue factor pre-mrna modulates the thrombogenecity of human platelets
topic Brief Definitive Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118136/
https://www.ncbi.nlm.nih.gov/pubmed/17060476
http://dx.doi.org/10.1084/jem.20061302
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