title: Dissociation of SERPINE1 mRNA from the translational repressor proteins Ago2 and TIA-1 upon platelet activation.
abstract: Platelets play an important role in haemostasis, as well as in thrombosis and coagulation processes. They harbour a wide variety of messenger RNAs (mRNAs), that can template de novo protein synthesis, and an abundant array of microRNAs, which are known to mediate mRNA translational repression through proteins of the Argonaute (Ago) family. The relationship between platelet microRNAs and proteins capable of mediating translational repression, however, remains unclear. Here, we report that half of platelet microRNAs is associated to mRNA-regulatory Ago2 protein complexes, in various proportions. Associated to these Ago2 complexes are platelet mRNAs known to support de novo protein synthesis. Reporter gene activity assays confirmed the capacity of the platelet microRNAs, found to be associated to Ago2 complexes, to regulate translation of these platelet mRNAs through their 3'UTR. Neither the microRNA repertoire nor the microRNA composition of Ago2 complexes of human platelets changed upon activation with thrombin. However, under conditions favoring de novo synthesis of Plasminogen Activator Inhibitor-1 (PAI-1) protein, we documented a rapid dissociation of the encoding platelet SERPINE1 mRNA from Ago2 protein complexes as well as from the translational repressor protein T-cell-restricted intracellular antigen-1 (TIA-1). These findings are consistent with a scenario by which lifting of the repressive effects of Ago2 and TIA-1 protein complexes, involving a rearrangement of proteinmRNA complexes rather than disassembly of Ago2microRNA complexes, would allow translation of SERPINE1 mRNA into PAI-1 in response to platelet activation.
authors: Aurélie
authors: A
authors: Corduan
authors: Hélène
authors: H
authors: Plé
authors: Benoit
authors: B
authors: Laffont
authors: Thérèse
authors: T
authors: Wallon
authors: Isabelle
authors: I
authors: Plante
authors: Patricia
authors: P
authors: Landry
authors: Dr. Patrick Provost, CHUQ Research Center/CHUL, 2705 Blvd Laurier, Room T1-65, Quebec, QC G1V 4G2, Canada, Tel.: +1 418 525 4444 (ext. 48842), E-mail: patrick.provost@crchudequebec.ulaval.ca.
authors: Patrick
authors: P
authors: Provost
mesh_terms: D020413:3' Untranslated Regions; D060565:Argonaute Proteins / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D047468:Immunoprecipitation; D035683:MicroRNAs / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D015539:Platelet Activation / Q000235:genetics; D039102:Poly(A)-Binding Proteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D000074019:T-Cell Intracellular Antigen-1; D013917:Thrombin / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C466422:AGO2 protein, human; D060565:Argonaute Proteins; D035683:MicroRNAs; D017395:Plasminogen Activator Inhibitor 1; D039102:Poly(A)-Binding Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C051321:SERPINE1 protein, human; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; D013917:Thrombin
keywords: Argonaute 2; Plasminogen activator inhibitor-1 (PAI-1); Platelet; mRNA; microRNA