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Routine Screening Method for Microparticles in Platelet Transfusions
Published on: January 31, 2018
The repertoire and features of human platelet microRNAs
Hélène Plé1, Patricia Landry, Ashley Benham
1Centre Hospitalier Universitaire de Québec Research Center/Centre hospitalier de l'Université Laval, Quebec, Quebec, Canada.
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.
Insights
Human platelets contain a diverse range of microRNAs (miRNAs), including novel sequences and modified forms. This study characterizes platelet miRNAs, revealing their complexity and potential regulatory roles in hemostasis and thrombosis.
Area of Science:
- Molecular Biology
- Hematology
- Genomics
Background:
- Platelets play key roles in hemostasis and thrombotic disorders.
- Platelets possess a diverse messenger RNA (mRNA) transcriptome and microRNAs (miRNAs).
- Platelet mRNA regulation by miRNAs is suggested but not fully understood.
Purpose of the Study:
- To elucidate the complete repertoire and features of human platelet microRNAs (miRNAs).
- To investigate post-transcriptional modifications and isoforms of platelet miRNAs.
- To establish a foundation for understanding the role of platelet miRNAs.
Main Methods:
- High-throughput sequencing of human platelet small RNAs.
- In vitro enzymatic assays to study miRNA uridylation.
- Bioinformatic analysis to identify miRNA sequences and isoforms (isomiRs).
Main Results:
- Detected over 492 mature miRNAs and identified 40 novel miRNA sequences in human platelets.
- Observed post-transcriptional modifications, including terminal adenylation and uridylation, with evidence of TUT4 enzyme activity.
- Identified numerous microRNA isoforms (isomiRs) from imprecise Drosha/Dicer processing, some with altered mRNA targeting capabilities.
Conclusions:
- Human platelets harbor a diverse and complex miRNA repertoire.
- Platelet miRNAs undergo post-transcriptional modifications similar to nucleated cells.
- This characterization is crucial for understanding the intraplatelet and extraplatelet functions of platelet miRNAs.
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