Abstract
Platelets, anucleated cells with a central role in hemostasis and inflammation, contain messenger RNAs and microRNAs of unknown functionality and clinical relevance. Historically, platelet RNA was viewed as merely a remnant of platelet biogenesis; however, several studies now refute this assumption. Studies have shown that platelets can actively translate RNA to protein and that specific RNA profiles correlate with select human clinical phenotypes. These studies support a more fluid role for platelet RNA in platelet function and disease development. Our lab and others have recently studied the platelet’s unique ability to transfer RNA to recipient cells and the effect this transfer has on the recipient cells’ functions. This transfer may represent a previously unknown form of vascular cell communication and modulation. Unlike the well-characterized thrombotic properties of platelets, the nature and purpose of platelet RNA transfer has not been determined, partly due to limitations in techniques used to manipulate platelet RNA profiles. Defining the mechanism of RNA transfer and its role in the vascular system will allow for the better understanding of how platelets function in both their traditional thrombotic role and non-traditional functions, potentially having widespread implications in several fields.
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References
Jurk K, Kehrel BE (2005) Platelets: physiology and biochemistry. Semin Thromb Hemost 31(4):381–392. doi:10.1055/s-2005-916671
Zimmerman GA, Weyrich AS (2008) Signal-dependent protein synthesis by activated platelets: new pathways to altered phenotype and function. Arterioscler Thromb Vasc Biol 28(3):s17–s24. doi:10.1161/ATVBAHA.107.160218
Bugert P, Dugrillon A, Gunaydin A, Eichler H, Kluter H (2003) Messenger RNA profiling of human platelets by microarray hybridization. Thromb Haemost 90(4):738–748. doi:10.1267/THRO03040738
Gnatenko DV, Dunn JJ, McCorkle SR, Weissmann D, Perrotta PL, Bahou WF (2003) Transcript profiling of human platelets using microarray and serial analysis of gene expression. Blood 101(6):2285–2293. doi:10.1182/blood-2002-09-2797
Bray PF, McKenzie SE, Edelstein LC, Nagalla S, Delgrosso K, Ertel A, Kupper J, Jing Y, Londin E, Loher P, Chen HW, Fortina P, Rigoutsos I (2013) The complex transcriptional landscape of the anucleate human platelet. BMC Genomics 14(1):1. doi:10.1186/1471-2164-14-1
Rowley JW, Oler AJ, Tolley ND, Hunter BN, Low EN, Nix DA, Yost CC, Zimmerman GA, Weyrich AS (2011) Genome-wide RNA-seq analysis of human and mouse platelet transcriptomes. Blood 118(14):e101–e111. doi:10.1182/blood-2011-03-339705
Freedman JE, Larson MG, Tanriverdi K, O’Donnell CJ, Morin K, Hakanson AS, Vasan RS, Johnson AD, Iafrati MD, Benjamin EJ (2010) Relation of platelet and leukocyte inflammatory transcripts to body mass index in the framingham heart study. Circulation 122(2):119–129. doi:10.1161/CIRCULATIONAHA.109.928192
Gnatenko DV, Cupit LD, Huang EC, Dhundale A, Perrotta PL, Bahou WF (2005) Platelets express steroidogenic 17beta-hydroxysteroid dehydrogenases. Distinct profiles predict the essential thrombocythemic phenotype. Thromb Haemost 94(2):412–421. doi:05080412
Gnatenko DV, Zhu W, Xu X, Samuel ET, Monaghan M, Zarrabi MH, Kim C, Dhundale A, Bahou WF (2010) Class prediction models of thrombocytosis using genetic biomarkers. Blood 115(1):7–14. doi:10.1182/blood-2009-05-224477
Lood C, Amisten S, Gullstrand B, Jonsen A, Allhorn M, Truedsson L, Sturfelt G, Erlinge D, Bengtsson AA (2010) Platelet transcriptional profile and protein expression in patients with systemic lupus erythematosus: up-regulation of the type I interferon system is strongly associated with vascular disease. Blood 116(11):1951–1957. doi:10.1182/blood-2010-03-274605
Nagalla S, Bray PF (2010) Platelet RNA chips dip into thrombocytosis. Blood 115(1):2–3. doi:10.1182/blood-2009-10-246405
Raghavachari N, Xu X, Harris A, Villagra J, Logun C, Barb J, Solomon MA, Suffredini AF, Danner RL, Kato G, Munson PJ, Morris SM Jr, Gladwin MT (2007) Amplified expression profiling of platelet transcriptome reveals changes in arginine metabolic pathways in patients with sickle cell disease. Circulation 115(12):1551–1562. doi:10.1161/CIRCULATIONAHA.106.658641
Risitano A, Beaulieu LM, Vitseva O, Freedman JE (2012) Platelets and platelet-like particles mediate intercellular RNA transfer. Blood 119(26):6288–6295. doi:10.1182/blood-2011-12-396440
Aatonen M, Gronholm M, Siljander PR (2012) Platelet-derived microvesicles: multitalented participants in intercellular communication. Semin Thromb Hemost 38(1):102–113. doi:10.1055/s-0031-1300956
Heijnen HF, Schiel AE, Fijnheer R, Geuze HJ, Sixma JJ (1999) Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha-granules. Blood 94(11):3791–3799
Montecalvo A, Larregina AT, Shufesky WJ, Stolz DB, Sullivan ML, Karlsson JM, Baty CJ, Gibson GA, Erdos G, Wang Z, Milosevic J, Tkacheva OA, Divito SJ, Jordan R, Lyons-Weiler J, Watkins SC, Morelli AE (2012) Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood 119(3):756–766. doi:10.1182/blood-2011-02-338004
Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9(6):654–659. doi:10.1038/ncb1596
Wahlgren J, De LKT, Brisslert M, Vaziri Sani F, Telemo E, Sunnerhagen P, Valadi H (2012) Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes. Nucleic Acids Res 40(17):e130. doi:10.1093/nar/gks463
Patel SR, Hartwig JH, Italiano JE Jr (2005) The biogenesis of platelets from megakaryocyte proplatelets. J Clin Invest 115(12):3348–3354. doi:10.1172/JCI26891
Takeuchi K, Satoh M, Kuno H, Yoshida T, Kondo H, Takeuchi M (1998) Platelet-like particle formation in the human megakaryoblastic leukaemia cell lines, MEG-01 and MEG-01 s. Br J Haematol 100(2):436–444
Stratz C, Nuhrenberg TG, Binder H, Valina CM, Trenk D, Hochholzer W, Neumann FJ, Fiebich BL (2012) Micro-array profiling exhibits remarkable intra-individual stability of human platelet micro-RNA. Thromb Haemost 107(4):634–641. doi:10.1160/TH11-10-0742
Huang Y, Shen XJ, Zou Q, Wang SP, Tang SM, Zhang GZ (2011) Biological functions of microRNAs: a review. J Physiol Biochem 67(1):129–139. doi:10.1007/s13105-010-0050-6
Gidlöf O, van der Brug M, Ohman J, Gilje P, Olde B, Wahlestedt C, Erlinge D (2013) Platelets activated during myocardial infarction release functional miRNA, which can be taken up by endothelial cells and regulate ICAM1 expression. Blood 121(19):3908–3917. doi:10.1182/blood-2012-10-461798
Baj-Krzyworzeka M, Szatanek R, Weglarczyk K, Baran J, Urbanowicz B, Branski P, Ratajczak MZ, Zembala M (2006) Tumour-derived microvesicles carry several surface determinants and mRNA of tumour cells and transfer some of these determinants to monocytes. Cancer Immunol Immunother 55(7):808–818. doi:10.1007/s00262-005-0075-9
Laffont B, Corduan A, Ple H, Duchez AC, Cloutier N, Boilard E, Provost P (2013) Activated platelets can deliver mRNA regulatory Ago2bulletmicroRNA complexes to endothelial cells via microparticles. Blood 122(2):253–261. doi:10.1182/blood-2013-03-492801
Acknowledgments
This work was partially supported by RFA-HL-12-008 and RFA-RM-12-013 (JEF).
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Clancy, L., Freedman, J.E. New paradigms in thrombosis: novel mediators and biomarkers platelet RNA transfer. J Thromb Thrombolysis 37, 12–16 (2014). https://doi.org/10.1007/s11239-013-1001-1
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DOI: https://doi.org/10.1007/s11239-013-1001-1