title: The repertoire and features of human platelet microRNAs.
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.
authors.affiliation: Centre Hospitalier Universitaire de Québec Research Center/Centre hospitalier de l'Université Laval, Quebec, Quebec, Canada.
authors.forename: Hélène
authors.initials: H
authors.lastname: Plé
authors.forename: Patricia
authors.initials: P
authors.lastname: Landry
authors.forename: Ashley
authors.initials: A
authors.lastname: Benham
authors.forename: Cristian
authors.initials: C
authors.lastname: Coarfa
authors.forename: Preethi H
authors.initials: PH
authors.lastname: Gunaratne
authors.forename: Patrick
authors.initials: P
authors.lastname: Provost
mesh_terms: D001483:Base Sequence; D001792:Blood Platelets / Q000378:metabolism*; D004253:DNA Nucleotidylexotransferase / Q000378:metabolism; D020869:Gene Expression Profiling; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D058977:Molecular Sequence Annotation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics
chemical_list: D035683:MicroRNAs; C544302:Mirn140 microRNA, human; D020033:Protein Isoforms; D012322:RNA Precursors; D004253:DNA Nucleotidylexotransferase