1. Dissociation of SERPINE1 mRNA from the translational repressor proteins Ago2 and TIA-1 upon platelet activation
- Author
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Patricia Landry, Hélène Plé, Thérèse Wallon, Benoit Laffont, Isabelle Plante, Patrick Provost, and Aurélie Corduan
- Subjects
Blood Platelets ,0301 basic medicine ,030204 cardiovascular system & hematology ,Biology ,Poly(A)-Binding Proteins ,Polymerase Chain Reaction ,03 medical and health sciences ,0302 clinical medicine ,Thrombin ,Plasminogen Activator Inhibitor 1 ,microRNA ,medicine ,Protein biosynthesis ,Humans ,Immunoprecipitation ,Platelet ,RNA, Messenger ,Platelet activation ,3' Untranslated Regions ,Reporter gene ,Messenger RNA ,RNA-Binding Proteins ,Hematology ,Argonaute ,Flow Cytometry ,Platelet Activation ,T-Cell Intracellular Antigen-1 ,Repressor Proteins ,MicroRNAs ,030104 developmental biology ,Gene Expression Regulation ,Biochemistry ,Protein Biosynthesis ,Argonaute Proteins ,medicine.drug - Abstract
SummaryPlatelets 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 protein•mRNA complexes rather than disassembly of Ago2•microRNA complexes, would allow translation of SERPINE1 mRNA into PAI-1 in response to platelet activation.
- Published
- 2015