Download PDF
Thromb Haemost 2012; 108(04): 599-604
DOI: 10.1160/TH12-03-0211
Theme Issue Article
Schattauer GmbH

MicroRNAs in platelet biogenesis and function

Seema Dangwal
1   Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany
,
Thomas Thum
1   Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany
2   Centre for Clinical and Basic Research, IRCCS San Raffaele, Rome, Italy
› Author Affiliations
Further Information

Publication History

Received: 31 March 2012

Accepted: 03 May 2012

Publication Date:
29 November 2017 (online)

Also available at
    Permissions and Reprints

Summary

Platelets are important to maintain primary haemostasis and play a key role in pathology of thrombotic and occlusive vascular disorders such as acute coronary syndrome or stroke. Despite of lacking a nucleus and genomic DNA, platelets possess diverse types of RNAs, ranging from protein coding messenger RNAs to small non-coding RNAs inherited from their parent megakaryocytes. Indeed, platelets are capable of using their own translational machinery to synthesise proteins upon their activation suggesting the possibility of post-transcriptional gene regulation in platelets. MicroRNAs (miRNAs) are highly conserved, tiny non-coding RNAs exhibiting a fine-tune control of protein expression by complementary sequence recognition, binding and translational repression of protein coding mRNA transcripts. Multiple functional aspects of miRNAs as well as their expression in platelets or megakaryocytes underscore a role in platelet biology. Changes in miRNA expression patterns have been noted during platelet genesis and activation. In the present review we highlight recently identified megakaryocytic/platelet miRNAs and discuss their role in platelet biogenesis and functions essential to maintain haemostasis in the body.

Keywords

Platelet reactivity - megakaryocytopoiesis - platelet miRNA - P2Y12
 

  • References

  • 1 Broos K, Feys HB, De Meyer SF. et al. Platelets at work in primary hemostasis. Blood Rev 2011; 25: 155-167.
    CrossrefPubMedGoogle Scholar
  • 2 Ho-Tin-Noe B, Demers M, Wagner DD. How platelets safeguard vascular integrity. J Thromb Haemost 2011; 09 (Suppl. 01) 56-65.
    CrossrefPubMedGoogle Scholar
  • 3 Kottke-Marchant K. Importance of platelets and platelet response in acute coronary syndromes. Cleveland Clinic J Med 2009; 76 (Suppl. 01) S2-7.
    PubMedGoogle Scholar
  • 4 Boilard E, Nigrovic PA, Larabee K. et al. Platelets amplify inflammation in arthritis via collagen-dependent microparticle production. Science 2010; 327: 580-583.
    CrossrefPubMedGoogle Scholar
  • 5 Nurden AT. Platelets, inflammation and tissue regeneration. Thromb Haemost 2011; 105 (Suppl. 01) S13-33.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Jain S, Harris J, Ware J. Platelets: linking hemostasis and cancer. Arterioscl Thromb Vasc Biol 2010; 30: 2362-2367.
    CrossrefPubMedGoogle Scholar
  • 7 Avecilla ST, Hattori K, Heissig B. et al. Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis. Nature Med 2004; 10: 64-71.
    CrossrefPubMedGoogle Scholar
  • 8 Patel SR, Hartwig Jr JHEIJ. The biogenesis of platelets from megakaryocyte proplatelets. J Clin Invest 2005; 115: 3348-3354.
    CrossrefPubMedGoogle Scholar
  • 9 Deutsch VR, Tomer A. Megakaryocyte development and platelet production. Br J Haematol 2006; 134: 453-466.
    CrossrefPubMedGoogle Scholar
  • 10 Kaushansky K. The molecular mechanisms that control thrombopoiesis. J Clin Invest 2005; 115: 3339-3347.
    CrossrefPubMedGoogle Scholar
  • 11 Denis MM, Tolley ND, Bunting M. et al. Escaping the nuclear confines: signal-dependent pre-mRNA splicing in anucleate platelets. Cell 2005; 122: 379-391.
    CrossrefPubMedGoogle Scholar
  • 12 Weyrich AS, Schwertz H, Kraiss LW. et al. Protein synthesis by platelets: historical and new perspectives. J Thromb Haemost 2009; 07: 241-246.
    CrossrefPubMedGoogle Scholar
  • 13 Thon JN, Devine DV. Translation of glycoprotein IIIa in stored blood platelets. Transfusion 2007; 47: 2260-2270.
    CrossrefPubMedGoogle Scholar
  • 14 Landry P, Plante I, Ouellet DL. et al. Existence of a microRNA pathway in anucleate platelets. Nature Struct Mol Biol 2009; 16: 961-966.
    CrossrefPubMedGoogle Scholar
  • 15 Zimmerman GA, Weyrich AS. Signal-dependent protein synthesis by activated platelets: new pathways to altered phenotype and function. Arterioscler Thromb Vasc Biol 2008; 28: s17-24.
    CrossrefPubMedGoogle Scholar
  • 16 Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116: 281-297.
    CrossrefPubMedGoogle Scholar
  • 17 Wightman B, Ha I, Ruvkun G. Post-transcriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 1993; 75: 855-862.
    CrossrefPubMedGoogle Scholar
  • 18 Lee RC, Feinbaum RL, Ambros V The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993; 75: 843-854.
    CrossrefPubMedGoogle Scholar
  • 19 Thum T, Galuppo P, Wolf C. et al. MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failure. Circulation 2007; 116: 258-267.
    CrossrefPubMedGoogle Scholar
  • 20 Fiedler J, Jazbutyte V, Kirchmaier BC. et al. MicroRNA-24 regulates vascularity after myocardial infarction. Circulation 2011; 124: 720-730.
    CrossrefPubMedGoogle Scholar
  • 21 Thum T, Gross C, Fiedler J. et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature 2008; 456: 980-984.
    CrossrefPubMedGoogle Scholar
  • 22 Chen C, Ridzon DA, Broomer AJ. et al. Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res 2005; 33: e179.
    CrossrefPubMedGoogle Scholar
  • 23 Dangwal S, Bang C, Thum T. Novel techniques and targets in cardiovascular microRNA research. Cardiovasc Res 2011; 93: 545-554.
    PubMedGoogle Scholar
  • 24 Dittrich M, Birschmann I, Pfrang J. et al. Analysis of SAGE data in human platelets: features of the transcriptome in an anucleate cell. Thromb Haemost 2006; 95: 643-651.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Bauersachs J, Thum T. Biogenesis and Regulation of Cardiovascular MicroRNAs. Circulation Res 2011; 109: 334-347.
    CrossrefPubMedGoogle Scholar
  • 26 Lee Y, Ahn C, Han J. et al. The nuclear RNase III Drosha initiates microRNA processing. Nature 2003; 425: 415-419.
    CrossrefPubMedGoogle Scholar
  • 27 Gregory RI, Yan KP, Amuthan G. et al. The Microprocessor complex mediates the genesis of microRNAs. Nature 2004; 432: 235-240.
    CrossrefPubMedGoogle Scholar
  • 28 Chendrimada TP, Gregory RI, Kumaraswamy E. et al. TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Nature 2005; 436: 740-744.
    CrossrefPubMedGoogle Scholar
  • 29 Small EM, Olson EN. Pervasive roles of microRNAs in cardiovascular biology. Nature 2011; 469: 336-342.
    CrossrefPubMedGoogle Scholar
  • 30 Shyu AB, Wilkinson MF, van Hoof A. Messenger RNA regulation: to translate or to degrade. EMBO J 2008; 27: 471-481.
    CrossrefPubMedGoogle Scholar
  • 31 Guo H, Ingolia NT, Weissman JS. et al. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 2010; 466: 835-840.
    CrossrefPubMedGoogle Scholar
  • 32 Nagalla S, Shaw C, Kong X. et al. Platelet microRNA-mRNA coexpression profiles correlate with platelet reactivity. Blood 2011; 117: 5189-5197.
    CrossrefPubMedGoogle Scholar
  • 33 Hollopeter G, Jantzen HM, Vincent D. et al. Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature 2001; 409: 202-207.
    CrossrefPubMedGoogle Scholar
  • 34 Wihlborg AK, Wang L, Braun OO. et al. ADP receptor P2Y12 is expressed in vascular smooth muscle cells and stimulates contraction in human blood vessels. Arterioscler Thromb Vasc Biol 2004; 24: 1810-1815.
    CrossrefPubMedGoogle Scholar
  • 35 Haynes SE, Hollopeter G, Yang G. et al. The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat Neurosci 2006; 09: 1512-1519.
    CrossrefPubMedGoogle Scholar
  • 36 Dorsam RT, Kunapuli SP. Central role of the P2Y12 receptor in platelet activation. J Clin Invest 2004; 113: 340-345.
    CrossrefPubMedGoogle Scholar
  • 37 Hechler B, Gachet C. P2 receptors and platelet function. Purinergic Signal 2011; 07: 293-303.
    CrossrefPubMedGoogle Scholar
  • 38 Garzon R, Pichiorri F, Palumbo T. et al. MicroRNA fingerprints during human megakaryocytopoiesis. Proc Natl Acad Sci USA 2006; 103: 5078-5083.
    CrossrefPubMedGoogle Scholar
  • 39 Ichimura A, Ruike Y, Terasawa K. et al. MicroRNA-34a inhibits cell proliferation by repressing mitogen-activated protein kinase kinase 1 during megakaryocytic differentiation of K562 cells. Mol Pharmacol 2010; 77: 1016-1024.
    CrossrefPubMedGoogle Scholar
  • 40 Navarro F, Gutman D, Meire E. et al. miR-34a contributes to megakaryocytic differentiation of K562 cells independently of p53. Blood 2009; 114: 2181-2192.
    CrossrefPubMedGoogle Scholar
  • 41 Georgantas 3rd RW, Hildreth R, Morisot S. et al. CD34+ hematopoietic stem-progenitor cell microRNA expression and function: a circuit diagram of differentiation control. Proc Natl Acad Sci USA 2007; 104: 2750-275.
    CrossrefPubMedGoogle Scholar
  • 42 Romania P, Lulli V, Pelosi E. et al. MicroRNA 155 modulates megakaryopoiesis at progenitor and precursor level by targeting Ets-1 and Meis1 transcription factors. Br J Haematol 2008; 143: 570-580.
    CrossrefPubMedGoogle Scholar
  • 43 O'Connell RM, Rao DS, Chaudhuri AA. et al. Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder. J Exp Med 2008; 205: 585-594.
    CrossrefPubMedGoogle Scholar
  • 44 Lu J, Guo S, Ebert BL. et al. MicroRNA-mediated control of cell fate in megakaryocyte-erythrocyte progenitors. Develop Cell 2008; 14: 843-853.
    CrossrefPubMedGoogle Scholar
  • 45 Barroga CF, Pham H, Kaushansky K. Thrombopoietin regulates c-Myb expression by modulating micro RNA 150 expression. Exp Hematol 2008; 36: 1585-1592.
    CrossrefPubMedGoogle Scholar
  • 46 Opalinska JB, Bersenev A, Zhang Z. et al. MicroRNA expression in maturing murine megakaryocytes. Blood 2010; 116: e128-138.
    CrossrefPubMedGoogle Scholar
  • 47 Labbaye C, Spinello I, Quaranta MT. et al. A three-step pathway comprising PLZF/ miR-146a/CXCR4 controls megakaryopoiesis. Nature Cell Biol 2008; 10: 788-801.
    CrossrefPubMedGoogle Scholar
  • 48 Starczynowski DT, Kuchenbauer F, Argiropoulos B. et al. Identification of miR-145 and miR-146a as mediators of the 5q- syndrome phenotype. Nature Med 2010; 16: 49-58.
    CrossrefPubMedGoogle Scholar
  • 49 Starczynowski DT, Kuchenbauer F, Wegrzyn J. et al. MicroRNA-146a disrupts hematopoietic differentiation and survival. Exp Hematol 2011; 39: 167 178 e4.
    CrossrefPubMedGoogle Scholar
  • 50 Kondkar AA, Bray MS, Leal SM. et al. VAMP8/endobrevin is overexpressed in hyperreactive human platelets: suggested role for platelet microRNA. J Thromb Haemost 2010; 08: 369-378.
    CrossrefPubMedGoogle Scholar
  • 51 Osman A, Falker K. Characterization of human platelet microRNA by quantitative PCR coupled with an annotation network for predicted target genes. Platelets 2011; 22: 433-41.
    CrossrefPubMedGoogle Scholar
  • 52 Diehl P, Fricke A, Sander L. et al. Microparticles: major transport vehicles for distinct microRNAs in circulation. Cardiovasc Res 2012; 93: 633-644.
    CrossrefPubMedGoogle Scholar
  • 53 Rautou PE, Vion AC, Amabile N. et al. Microparticles, vascular function, and atherothrombosis. Circulation Res 2011; 109: 593-606.
    CrossrefPubMedGoogle Scholar
  • 54 Zampetaki A, Mayr M. MicroRNAs in Vascular and Metabolic Disease. Circ Res 2012; 110: 508-522.
    CrossrefPubMedGoogle Scholar
  • 55 Schedel A, Rolf N. Genome-wide platelet RNA profiling in clinical samples. Methods Mol Biol 2009; 496: 273-283.
    PubMedGoogle Scholar
  • 56 Amisten S. A rapid and efficient platelet purification protocol for platelet gene expression studies. Methods Mol Biol 2012; 788: 155-172.
    PubMedGoogle Scholar
  • 57 Hong W, Kondkar AA, Nagalla S. et al. Transfection of human platelets with short interfering RNA. Clin Transl Sci 2011; 04: 180-182.
    CrossrefPubMedGoogle Scholar
  • 58 Sondermeijer BM, Bakker A, Halliani A. et al. Platelets in patients with premature coronary artery disease exhibit upregulation of miRNA340* and miRNA624*. PloS One 2010; 06: e25946.
    PubMedGoogle Scholar
  • 59 Girardot M, Pecquet C, Boukour S. et al. miR-28 is a thrombopoietin receptor targeting microRNA detected in a fraction of myeloproliferative neoplasm patient platelets. Blood 2010; 116: 437-445.
    CrossrefPubMedGoogle Scholar