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ABSTRACT
Circular RNAs (circRNAs) are a novel class of noncoding RNAs present in all eukaryotic cells investigated so far and generated by a special mode of alternative splicing of pre-mRNAs. Thereby, single exons, or multiple adjacent and spliced exons, are released in a circular form. CircRNAs are cell-type specifically expressed, are unusually stable, and can be found in various body fluids such as blood and saliva. Here we analysed circRNAs and the corresponding linear splice isoforms from human platelets, where circRNAs are particularly abundant, compared with other hematopoietic cell types. In addition, we isolated extracellular vesicles from purified and in vitro activated human platelets, using density-gradient centrifugation, followed by RNA-seq analysis for circRNA detection. We could demonstrate that circRNAs are packaged and released within both types of vesicles (microvesicles and exosomes) derived from platelets. Interestingly, we observed a selective release of circRNAs into the vesicles, suggesting a specific sorting mechanism. In sum, circRNAs represent yet another class of extracellular RNAs that circulate in the body and may be involved in signalling pathways. Since platelets are essential for central physiological processes such as haemostasis, wound healing, inflammation and cancer metastasis, these findings should greatly extend the potential of circRNAs as prognostic and diagnostic biomarkers.
ARTICLE HISTORY
Received 14 June 2017
Accepted 5 December 2017
KEYWORDS
CircRNAs; extracellular vesicles; exosomes; microvesicles; platelets
Introduction
Thrombocytes - also referred as platelets - belong to the corpuscular components of mammalian blood and are essential for central physiological processes such as haemostasis (see, for review, [1]). Platelets are peculiar in that they are, first, relatively short-lived (~7 days half-life); second, they are the smallest cells of blood, and third, although without a nucleus, they exhibit active RNA metabolism and are translationally active [2-5]. During thrombopoiesis, anucleated platelets are derived from megakaryocytes in the bone marrow and are released into the bloodstream. In the absence of de novo RNA synthesis, platelets mirror the particular expression status of the megakaryocyte at the specific time point they are generated. To orchestrate all their tasks, platelets release - in addition to chemokines and cytokines - two major types of extracellular vesicles (EVs) into the bloodstream, which can be internalised by different target cells, such as endothelial cells [6,7]. In fact, platelets release massive amounts...