Dissociation of SERPINE1 mRNA from the translational repressor proteins Ago2 and TIA-1 upon platelet activation

Authors: Corduan, AuréliePlé, HélèneLaffont, BenoitWallon, ThérèsePlante, IsabelleLandry, PatriciaProvost, Patrick
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
Document Type: Article de recherche
Issue Date: 12 February 2014
Open Access Date: Restricted access
Document version: VoR
Permalink: http://hdl.handle.net/20.500.11794/34250
This document was published in: Thrombosis and haemostasis, Vol. 113 (5), 1046–1059 (2015)
http://dx.doi.org/10.1160/TH14-07-0622
Thieme
Alternative version: 10.1160/TH14-07-0622
25673011
Collection:Articles publiés dans des revues avec comité de lecture

Files in this item:
Description SizeFormat 
29 Corduan SERPINE1 Ago2 TIA-1 TH 2015 copy.pdf
2.59 MBAdobe PDF    Request a copy
All documents in CorpusUL are protected by Copyright Act of Canada.