Abstract
Playing a central role in the maintenance of hemostasis as well as in thrombotic disorders, platelets contain a relatively diverse messenger RNA (mRNA) transcriptome as well as functional mRNA-regulatory microRNAs, suggesting that platelet mRNAs may be regulated by microRNAs. Here, we elucidated the complete repertoire and features of human platelet microRNAs by high-throughput sequencing. More than 492 different mature microRNAs were detected in human platelets, whereas the list of known human microRNAs was expanded further by the discovery of 40 novel microRNA sequences. As in nucleated cells, platelet microRNAs bear signs of post-transcriptional modifications, mainly terminal adenylation and uridylation. In vitro enzymatic assays demonstrated the ability of human platelets to uridylate microRNAs, which correlated with the presence of the uridyltransferase enzyme TUT4. We also detected numerous microRNA isoforms (isomiRs) resulting from imprecise Drosha and/or Dicer processing, in some cases more frequently than the reference microRNA sequence, including 5′ shifted isomiRs with redirected mRNA targeting abilities. This study unveils the existence of a relatively diverse and complex microRNA repertoire in human platelets, and represents a mandatory step towards elucidating the intraplatelet and extraplatelet role, function and importance of platelet microRNAs.
Highlights
Platelets play a central role in the maintenance of hemostasis as well as in thrombotic disorders
The length distribution analysis of the usable reads, obtained from the 2 different pools, revealed that more than 90% of the sequences were in the 19- to 24-nt window of RNA sizes, which is characteristic of microRNAs (Figure 1A)
This study presents the complete repertoire and features of human platelet microRNAs
Summary
Platelets play a central role in the maintenance of hemostasis as well as in thrombotic disorders. Forming a class of small, 19- to 24-nucleotide (nt) non-coding RNA species and known as master regulators of mRNA translation [13], microRNAs derive from the sequential processing of longer RNA precursors by the ribonucleases Drosha and Dicer, as reviewed recently [14,15,16]. One or both strands of microRNA duplexes are subsequently loaded into an effector ribonucleoprotein (microRNP) complex containing an Argonaute (Ago) protein. Predicted to regulate ,60% of the genes in human, microRNAs are believed to be involved in most, if not all, physiological and pathological processes; one can anticipate that microRNAs will play a significant role in health and disease
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