© Schattauer 2013 Hämostaseologie 1/2013 17 Review MicroRNAs in platelet physiology and pathology S. Dangwal; T. Thum Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany Keywords MicroRNAs Summary MicroRNAs (miRNAs), highly conserved, short (approx. 22 nucleotides) non-coding RNAs, exhibit a fine-tune control over gene expression by complementary sequence binding and translational repression of protein coding mRNA transcripts. Recently, the role of miRNAs has been increasingly in- vestigated in various physiological or patho- physiological events. Circulating platelets are crucial for coagu- lation physiology to maintain haemostatic balance and are involved in various pathol- ogies such as atherosclerosis and thrombo- sis. Anucleate platelets lack genomic DNA but inherit diverse array of functional coding or non-coding RNAs and translational machinery from their parent cells – mega- karyocytes enabling activated platelets to synthesize proteins which suggests the possi- bility of post transcriptional gene regulation in platelets. Expression of functionally active miRNAs in platelets changes during platelet activation indicating a role in platelet biology. Here, we present a review on recently ident- ified platelet miRNAs and their role in platelet physiology that is essential for main- taining haemostasis. Schlüsselwörter MicroRNAs Zusammenfassung MicroRNAs (miRNAs) sind evolutionär hoch- konservierte kurze (etwa 20 Nukleotide) nicht kodierende RNA Moleküle, die eine Kontrolle der Genexpression durch Bindung an komplementäre mRNA-Sequenzen und translationale Repression von Protein- kodierenden mRNA-Transkripten bewirken. MiRNAs sind an vielen physiologischen und pathophysiologischen Vorgängen des Körpers beteiligt. Zirkulierende Thrombozyten sind essenziell für die Balance der Blutgerinnung und auch bedeutend für die vaskuläre Integrität. Sie sind ebenso bei atherosklerotischen wie auch bei thrombotischen Erkrankungen involviert. Anuklären Thrombozyten fehlt genomische DNA, aber sie besitzen eine Anzahl funktio- nell kodierender aber auch nicht kodierender RNA-Moleküle. Des Weiteren besitzen Throm- bozyten eine funktionstüchtige translationa- le Maschinerie, die es ihnen erlaubt, Proteine zu synthetisieren – Prozesse, die wiederum über miRNAs reguliert werden. Die Bedeutung von nicht kodierenden micro- RNAs in der Regulation der Thrombozyten- funktion ist daher Gegenstand dieses Über- sichtsartikels. Correspondence to: Thomas Thum, MD, PhD Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Carl- Neuberg-Str. 1, 30625 Hannover, Germany Tel. +49/(0)511/532 52 73, Fax +49/(0)511/532 52 74 E-Mail: thum.thomas@mh-hannover.de Micro-RNA, Physiologie und Pathologie der Thrombozyten Hämostaseologie 2013; 33: 17–20 DOI:10.5482/HAMO-13-01-0002 Received: January 7, 2013 Accepted in revised form: January 17, 2013 MicroRNAs (miRNA) are small (21–23 nucleotides) non-coding RNAs regulating about two third of the mammalian protein coding genes at least in part by trans- lational repression (1). MiRNAs are in- creasingly shown to play vital role in cellu- lar development and various pathologies (2–7). Although most miRNAs expressed in multi-cellular organisms are well con- served throughout the animal kingdom (1) their expression varies in cellular content i. e. miRNA copy numbers (8) and tissue distribution patterns (5,9). Platelets, the circulating anucleate blood cells, are crucial to maintain haemostasis and safeguard vascular integrity (10, 11). If disturbed, the platelet reactivity associates with various pathologies leading to mor- bidity and mortality (12–15) such as • atherosclerosis, • occlusive or thrombotic cardiovascular disorders, • inflammation and • cancer. Platelets are released into circulation as cy- toplasmic fragments, originated from bone-marrow megakaryocytes through commitment of the multipotent stem cells to the megakaryocyte lineage, proliferation of the progenitors and terminal differenti- ation of megakaryocytes in a precisely con- trolled microenvironment (16, 17). Despite of lacking nucleus, platelets are able to translate inherited mRNAs into proteins (18, 19) for example synthesis of integrin- alpha 3 (glycoprotein-IIIa) protein, a fibri- nogen receptor involved in platelet aggre- gation, is observed during their preserva- tion (19, 20). Surprisingly, more than 32% of the human genes are represented as messenger RNA in circulating platelets. A strong correlation between platelet tran- scriptome and proteomic profile, in addi- tion to inherited functional translation ma- chinery e. g. rough endoplasmic reticulum, For personal or educational use only. No other uses without permission. All rights reserved. Downloaded from www.haemostaseologie-online.com on 2017-06-18 | IP: 54.191.40.80