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Existence of a microRNA pathway in anucleate platelets

Abstract

Platelets have a crucial role in the maintenance of hemostasis as well as in thrombosis and vessel occlusion, which underlie stroke and acute coronary syndromes. Anucleate platelets contain mRNAs and are capable of protein synthesis, raising the issue of how these mRNAs are regulated. Here we show that human platelets harbor an abundant and diverse array of microRNAs (miRNAs), which are known as key regulators of mRNA translation in other cell types. Further analyses revealed that platelets contain the Dicer and Argonaute 2 (Ago2) complexes, which function in the processing of exogenous miRNA precursors and the control of specific reporter transcripts, respectively. Detection of the receptor P2Y12 mRNA in Ago2 immunoprecipitates suggests that P2Y12 expression may be subjected to miRNA control in human platelets. Our study lends an additional level of complexity to the control of gene expression in these anucleate elements of the cardiovascular system.

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Figure 1: Human platelets contain an abundant and diverse array of miRNAs.
Figure 2: Platelets can synthesize miRNAs from pre-miRNAs.
Figure 3: Platelets harbor Ago2–miRNA effector complexes that are functionally competent in gene silencing.
Figure 4: Ago2–miR-223 complexes may regulate P2Y12 mRNA expression in platelets.

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Acknowledgements

We thank S. Picard (Université Laval) for providing the PRP and the CHUQ Research Center Computer Graphics Department for the illustrations. M.P.P. was supported by a doctoral studentship from Natural Sciences and Engineering Research Council of Canada (NSERC). G.R. and P.P. are supported by the Fonds de la Recherche en Santé du Québec (FRSQ). This work was supported by a Cardiovascular Research Award from Pfizer Canada Inc. and a Canadian Institutes of Health Research (CIHR)/Rx&D Collaborative Research Grant (IRO-86239) to P.P.

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P.P. conceived and coordinated the study; P.L., G.R. and P.P. designed and planned the experiments; P.L. led the project; P.L., I.P., D.L.O. and M.P.P. performed the experiments; all authors analyzed the data and edited/commented on the manuscript; P.P. wrote the manuscript.

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Correspondence to Patrick Provost.

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Landry, P., Plante, I., Ouellet, D. et al. Existence of a microRNA pathway in anucleate platelets. Nat Struct Mol Biol 16, 961–966 (2009). https://doi.org/10.1038/nsmb.1651

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