Platelets are critical blood cells involved in clotting. An early step in clot construction requires tissue factor (TF), but whether platelets make TF was unknown. New work by Schwertz et al. (page 2433) reveals that these nuclei-free cells doproduce TF by cytoplasmic splicing and further identify the kinase Clk1 as a splicing activator.
After injury to a blood vessel, platelets are the first cells on the scene to plug the hole. Platelets get activated by attachment to exposed collagen (amongst other things), and promote a TF-dependent coagulation cascade on their cell membranes. This ultimately results in large-scale fibrin production and the assembly of a tough fibrin meshwork over the platelet plug. TF is released from the injured tissue, but whether platelets themselves express TF is a debated question.
Schwertz et al. found that activated human platelets contained TF mRNA. Resting platelets instead contained unspliced TF pre-mRNA. Activation, the team showed, induced splicing and subsequent translation of TF in as little as 5 min.
Cytoplasmic splicing was described for the first time by this group a year ago. The precise mechanism is unknown, but splicing factor SF2/ASF was identified in platelet cytoplasms. In nucleated cells, Clk1 activates SF2/ASF by phosphorylation. Interrupting this modification, the team now shows, prevents processing of TF pre-mRNA.
A number of conditions lead to increased blood clotting. In recent unpublished work, the team found that platelets isolated from septic patients, in whom thrombosis occurs, are more prone to clotting and contain increased levels of spliced TF mRNA. Clk1-controlled splicing might thus be a good target for anticoagulation treatments. 
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