A tour through the transcriptional landscape of platelets.

The RNA code found within a platelet and alterations of that code continue to shed light onto the mechanistic underpinnings of platelet function and dysfunction. It is now known that features of messenger RNA (mRNA) in platelets mirror those of nucleated cells. This review serves as a tour guide for readers interested in developing a greater understanding of platelet mRNA. The tour provides an in-depth and interactive examination of platelet mRNA, especially in the context of next-generation RNA sequencing. At the end of the expedition, the reader will have a better grasp of the topography of platelet mRNA and how it impacts platelet function in health and disease.

[1]  A. Mast,et al.  Biology of tissue factor pathway inhibitor. , 2014, Blood.

[2]  C. Shaw,et al.  Human platelet microRNA-mRNA networks associated with age and gender revealed by integrated plateletomics. , 2014, Blood.

[3]  Jeffrey A. Thompson,et al.  Common features of microRNA target prediction tools , 2014, Front. Genet..

[4]  C. Shaw,et al.  The human platelet: strong transcriptome correlations among individuals associate weakly with the platelet proteome , 2014, Biology Direct.

[5]  J. Mcfarland,et al.  Human platelet antigens – 2013 , 2014, Vox sanguinis.

[6]  M. Wickens,et al.  Translation of Human Tissue Factor Pathway Inhibitor-&bgr; mRNA Is Controlled by Alternative Splicing Within the 5′ Untranslated Region , 2014, Arteriosclerosis, thrombosis, and vascular biology.

[7]  T. Lindahl,et al.  Next Generation Sequencing Analysis of Human Platelet PolyA+ mRNAs and rRNA-Depleted Total RNA , 2013, PloS one.

[8]  M. Kempers,et al.  A dominant-negative GFI1B mutation in the gray platelet syndrome. , 2013, New England Journal of Medicine.

[9]  C. Shaw,et al.  Racial Difference in Human Platelet PAR4 Reactivity Reflects Expression of PCTP and miR-376c , 2013, Nature Medicine.

[10]  D. McManus,et al.  Relationship Among Circulating Inflammatory Proteins, Platelet Gene Expression, and Cardiovascular Risk , 2013, Arteriosclerosis, thrombosis, and vascular biology.

[11]  Nicolas Servant,et al.  A comprehensive evaluation of normalization methods for Illumina high-throughput RNA sequencing data analysis , 2013, Briefings Bioinform..

[12]  Pedro G. Ferreira,et al.  Transcriptome and genome sequencing uncovers functional variation in humans , 2013, Nature.

[13]  C. Norbury Cytoplasmic RNA: a case of the tail wagging the dog , 2013, Nature Reviews Molecular Cell Biology.

[14]  L. Romão,et al.  Gene Expression Regulation by Upstream Open Reading Frames and Human Disease , 2013, PLoS genetics.

[15]  P. Provost,et al.  Activated platelets can deliver mRNA regulatory Ago2•microRNA complexes to endothelial cells via microparticles. , 2013, Blood.

[16]  P. Münzer,et al.  Thrombin-sensitive expression of the store operated Ca(2+) channel Orai1 in platelets. , 2013, Biochemical and biophysical research communications.

[17]  E Schaeffeler,et al.  Genetic variation of platelet function and pharmacology: An update of current knowledge , 2013, Thrombosis and Haemostasis.

[18]  A. Mast,et al.  Comparison of the inhibitory activities of human tissue factor pathway inhibitor (TFPI)α and TFPIβ , 2013, Journal of thrombosis and haemostasis : JTH.

[19]  B. Olde,et al.  Platelets activated during myocardial infarction release functional miRNA which can be taken up by endothelial cells and regulate ICAM1 expression , 2013, Blood.

[20]  C. Hayward,et al.  Genetic Loci Associated with Platelet Traits and Platelet Disorders , 2013, Seminars in Thrombosis & Hemostasis.

[21]  M. Mayr,et al.  MicroRNAs Within the Continuum of Postgenomics Biomarker Discovery , 2013, Arteriosclerosis, thrombosis, and vascular biology.

[22]  J. Jia,et al.  Regulation and dysregulation of 3'UTR-mediated translational control. , 2013, Current opinion in genetics & development.

[23]  I. Rigoutsos,et al.  The complex transcriptional landscape of the anucleate human platelet , 2013, BMC Genomics.

[24]  P. Gunaratne,et al.  The Repertoire and Features of Human Platelet microRNAs , 2012, PloS one.

[25]  Piero Carninci,et al.  Long non-coding antisense RNA controls Uchl1 translation through an embedded SINEB2 repeat , 2012, Nature.

[26]  A. Weyrich,et al.  Platelet mRNA: the meaning behind the message , 2012, Current opinion in hematology.

[27]  T. Kunicki,et al.  Genetic variants that affect platelet function , 2012, Current opinion in hematology.

[28]  David Haussler,et al.  The UCSC genome browser and associated tools , 2012, Briefings Bioinform..

[29]  G. Rousseau,et al.  Alteration of the platelet transcriptome in chronic kidney disease , 2012, Thrombosis and Haemostasis.

[30]  J. Freedman,et al.  Platelets and platelet-like particles mediate intercellular RNA transfer. , 2012, Blood.

[31]  Paul Lasko,et al.  Translational control in cellular and developmental processes , 2012, Nature Reviews Genetics.

[32]  B. Vojtesek,et al.  The role of the 3' untranslated region in post-transcriptional regulation of protein expression in mammalian cells. , 2012, RNA biology.

[33]  A. Kauskot,et al.  A novel mechanism of sustained platelet αIIbβ3 activation via PEAR1. , 2012, Blood.

[34]  Helga Thorvaldsdóttir,et al.  Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration , 2012, Briefings Bioinform..

[35]  L. Maquat,et al.  Regulation of cytoplasmic mRNA decay , 2012, Nature Reviews Genetics.

[36]  H. Binder,et al.  Micro-array profiling exhibits remarkable intra-individual stability of human platelet micro-RNA , 2012, Thrombosis and Haemostasis.

[37]  S. Gringhuis,et al.  Dectin-1 is an extracellular pathogen sensor for the induction and processing of IL-1β via a noncanonical caspase-8 inflammasome , 2012, Nature Immunology.

[38]  Christian Gieger,et al.  New gene functions in megakaryopoiesis and platelet formation , 2011, Nature.

[39]  Andrew J. Oler,et al.  Genome-wide RNA-seq analysis of human and mouse platelet transcriptomes. , 2011, Blood.

[40]  J. Parkinson,et al.  Mutations in NBEAL2, encoding a BEACH protein, cause gray platelet syndrome , 2011, Nature Genetics.

[41]  C. Gachet,et al.  P2 receptors and platelet function , 2011, Purinergic Signalling.

[42]  Gregory E. Jordan,et al.  Exome sequencing identifies NBEAL2 as the causative gene for Gray Platelet Syndrome , 2011, Nature Genetics.

[43]  J. Mullikin,et al.  NBEAL2 is mutated in Gray Platelet Syndrome and is required for biogenesis of platelet alpha-granules , 2011, Nature Genetics.

[44]  Cole Trapnell,et al.  Computational methods for transcriptome annotation and quantification using RNA-seq , 2011, Nature Methods.

[45]  Y. Tomiyama,et al.  [Effects of anticoagulants and storage temperature on immature platelet fraction % (IPF%) values in stored samples measured by the automated hematology analyzer, XE-5000--utility of CTAD-anticoagulation and room temperature storage]. , 2011, Rinsho byori. The Japanese journal of clinical pathology.

[46]  Fatih Ozsolak,et al.  RNA sequencing: advances, challenges and opportunities , 2011, Nature Reviews Genetics.

[47]  Chris I. Jones,et al.  Transcription profiling in human platelets reveals LRRFIP1 as a novel protein regulating platelet function. , 2010, Blood.

[48]  L. Edelstein,et al.  MicroRNAs in platelet production and activation. , 2010, Blood.

[49]  C. Shaw,et al.  Platelet microRNA-mRNA coexpression profiles correlate with platelet reactivity. , 2010, Blood.

[50]  Michael M. Mwangi,et al.  Transcriptome-wide sequencing reveals numerous APOBEC1 mRNA editing targets in transcript 3′ UTRs , 2010, Nature Structural &Molecular Biology.

[51]  T. Kunicki,et al.  The genetics of normal platelet reactivity. , 2010, Blood.

[52]  L. Truedsson,et al.  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. , 2010, Blood.

[53]  D. Devine,et al.  De novo protein synthesis in mature platelets: a consideration for transfusion medicine , 2010, Vox sanguinis.

[54]  Andrew D. Johnson,et al.  Relation of Platelet and Leukocyte Inflammatory Transcripts to Body Mass Index in the Framingham Heart Study , 2010, Circulation.

[55]  Nilanjan Chatterjee,et al.  Estimation of effect size distribution from genome-wide association studies and implications for future discoveries , 2010, Nature Genetics.

[56]  A. Ciccodicola,et al.  Uncovering the Complexity of Transcriptomes with RNA-Seq , 2010, Journal of biomedicine & biotechnology.

[57]  Andrew D. Johnson,et al.  Genome-wide meta-analyses identifies 7 loci associated with platelet aggregation in response to agonists , 2010, Nature genetics.

[58]  J. Brookfield,et al.  Q&A: Promise and pitfalls of genome-wide association studies , 2010, BMC Biology.

[59]  G. Blobe,et al.  Gfi-1B controls human erythroid and megakaryocytic differentiation by regulating TGF-beta signaling at the bipotent erythro-megakaryocytic progenitor stage. , 2010, Blood.

[60]  Joseph K. Pickrell,et al.  Understanding mechanisms underlying human gene expression variation with RNA sequencing , 2010, Nature.

[61]  Yusuke Nakamura,et al.  Genome-wide association study of hematological and biochemical traits in a Japanese population , 2010, Nature Genetics.

[62]  M. Monaghan,et al.  Class prediction models of thrombocytosis using genetic biomarkers. , 2010, Blood.

[63]  C. Wahlestedt,et al.  Regulatory roles of natural antisense transcripts , 2009, Nature Reviews Molecular Cell Biology.

[64]  G. Rousseau,et al.  Existence of a microRNA pathway in anucleate platelets , 2009, Nature Structural &Molecular Biology.

[65]  S. R. Wente,et al.  mRNA nuclear export at a glance , 2009, Journal of Cell Science.

[66]  G. Weigel,et al.  P‐selectin mRNA is maintained in platelet concentrates stored at 4°C , 2009, Transfusion.

[67]  A. Osei-Bimpong The effect of storage on the clinical utility of the immature platelet fraction , 2009, Hematology.

[68]  S. Steinhubl,et al.  G-Protein–Coupled Receptors as Signaling Targets for Antiplatelet Therapy , 2009, Arteriosclerosis, thrombosis, and vascular biology.

[69]  W. Gallagher,et al.  High-Throughput Proteomics Detection of Novel Splice Isoforms in Human Platelets , 2009, PloS one.

[70]  F. Costa,et al.  The impact of microRNAs and alternative splicing in pharmacogenomics , 2009, The Pharmacogenomics Journal.

[71]  B. Frey,et al.  Deep surveying of alternative splicing complexity in the human transcriptome by high-throughput sequencing , 2008, Nature Genetics.

[72]  E. Wagner,et al.  Metabolism and regulation of canonical histone mRNAs: life without a poly(A) tail , 2008, Nature Reviews Genetics.

[73]  Eric T. Wang,et al.  Alternative Isoform Regulation in Human Tissue Transcriptomes , 2008, Nature.

[74]  B. Williams,et al.  Mapping and quantifying mammalian transcriptomes by RNA-Seq , 2008, Nature Methods.

[75]  W. Filipowicz,et al.  Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? , 2008, Nature Reviews Genetics.

[76]  G. Steger,et al.  Alternative splicing of platelet cyclooxygenase-2 mRNA in patients after coronary artery bypass grafting , 2007, Thrombosis and Haemostasis.

[77]  Peter J. Munson,et al.  Amplified Expression Profiling of Platelet Transcriptome Reveals Changes in Arginine Metabolic Pathways in Patients With Sickle Cell Disease , 2007, Circulation.

[78]  A. Weyrich,et al.  mTOR-dependent synthesis of Bcl-3 controls the retraction of fibrin clots by activated human platelets. , 2007, Blood.

[79]  E. Hoffman,et al.  Decreased platelet expression of myosin regulatory light chain polypeptide (MYL9) and other genes with platelet dysfunction and CBFA2/RUNX1 mutation: insights from platelet expression profiling , 2007, Journal of thrombosis and haemostasis : JTH.

[80]  S. Kunapuli,et al.  Alternative splice variants of phospholipase C-β2 are expressed in platelets: Effect on Gαq-dependent activation and localization , 2007 .

[81]  Nigel Mackman,et al.  Signal-dependent splicing of tissue factor pre-mRNA modulates the thrombogenecity of human platelets , 2006, The Journal of experimental medicine.

[82]  P. Libby,et al.  Platelet Expression Profiling and Clinical Validation of Myeloid-Related Protein-14 as a Novel Determinant of Cardiovascular Events , 2006, Circulation.

[83]  T. Dandekar,et al.  Analysis of SAGE data in human platelets: Features of the transcriptome in an anucleate cell , 2006, Thrombosis and Haemostasis.

[84]  Karin Milde-Langosch,et al.  The Fos family of transcription factors and their role in tumourigenesis. , 2005, European journal of cancer.

[85]  K. Swoboda,et al.  Escaping the Nuclear Confines: Signal-Dependent Pre-mRNA Splicing in Anucleate Platelets , 2005, Cell.

[86]  Doron Lancet,et al.  Genome-wide midrange transcription profiles reveal expression level relationships in human tissue specification , 2005, Bioinform..

[87]  Anton J. Enright,et al.  Human MicroRNA Targets , 2004, PLoS biology.

[88]  C. Hagedorn,et al.  Purifying mRNAs with a high-affinity eIF4E mutant identifies the short 3′ poly(A) end phenotype , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[89]  S. Brenner,et al.  Evidence for the widespread coupling of alternative splicing and nonsense-mediated mRNA decay in humans , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[90]  E. Lai Micro RNAs are complementary to 3′ UTR sequence motifs that mediate negative post-transcriptional regulation , 2002, Nature Genetics.

[91]  Aaron J. Shatkin,et al.  The ends of the affair: Capping and polyadenylation , 2000, Nature Structural Biology.

[92]  S. Karpatkin,et al.  Identification of a family of alternatively spliced mRNA species of angiopoietin-1. , 2000, Blood.

[93]  O. Tikhomirov,et al.  Production of soluble P-selectin by platelets and endothelial cells. , 1999, Biochemistry. Biokhimiia.

[94]  Beverly H. Koller,et al.  Decreased platelet aggregation, increased bleeding time and resistance to thromboembolism in P2Y1-deficient mice , 1999, Nature Medicine.

[95]  S. Kunapuli,et al.  Molecular Basis for ADP-induced Platelet Activation , 1998, The Journal of Biological Chemistry.

[96]  M. D. Kim Human Platelet Antigens , 1996 .

[97]  M. Becchi,et al.  Occurrence and biological effects of cholesteryl sulfate on blood platelets. , 1995, Biochimica et biophysica acta.

[98]  B. Chong,et al.  Quantitation of soluble and membrane‐bound FC7RIIA (CD32A) mRNA in platelets and megakaryoblastic cell line (Meg‐01) , 1995, British journal of haematology.

[99]  K. Titani,et al.  Alternatively spliced isoform of P-selectin is present in vivo as a soluble molecule. , 1994, The Journal of biological chemistry.

[100]  J. Rosa,et al.  A new alternative transcript encodes a 60 kDa truncated form of integrin β3 , 1994 .

[101]  J. Fox Shedding of adhesion receptors from the surface of activated platelets. , 1994, Blood Coagulation and Fibrinolysis.

[102]  P. Newman,et al.  Structure of the human gene encoding granule membrane protein-140, a member of the selectin family of adhesion receptors for leukocytes. , 1990, The Journal of biological chemistry.

[103]  G. Roth,et al.  Circulating human blood platelets retain appreciable amounts of poly (A)+ RNA. , 1989, Biochemical and biophysical research communications.

[104]  J. Caen,et al.  An Abnormal Platelet Glycoprotein Pattern in Three Cases of Glanzmann's Thrombasthenia , 1974, British journal of haematology.

[105]  J. Freedman,et al.  New paradigms in thrombosis: novel mediators and biomarkers platelet RNA transfer , 2013, Journal of Thrombosis and Thrombolysis.

[106]  T. Thum,et al.  MicroRNAs in platelet physiology and pathology , 2013, Hämostaseologie.

[107]  L. Edelstein,et al.  Small RNAs as potential platelet therapeutics. , 2012, Handbook of experimental pharmacology.

[108]  M. Gerstein,et al.  RNA-Seq: a revolutionary tool for transcriptomics , 2009, Nature Reviews Genetics.

[109]  S. Kunapuli,et al.  Alternative splice variants of phospholipase C-beta2 are expressed in platelets: effect on Galphaq-dependent activation and localization. , 2007, Platelets.

[110]  A. W. van der Velden,et al.  The role of the 5' untranslated region of an mRNA in translation regulation during development. , 1999, The international journal of biochemistry & cell biology.

[111]  A. Houng,et al.  Identification and structure of activated-platelet protein-1, a protein with RNA-binding domain motifs that is expressed by activated platelets. , 1997, European journal of biochemistry.

[112]  J. Rosa,et al.  A new alternative transcript encodes a 60 kDa truncated form of integrin beta 3. , 1994, The Biochemical journal.

[113]  R. McEver Properties of GMP-140, an inducible granule membrane protein of platelets and endothelium. , 1990, Blood cells.

[114]  McEver Rp Properties of GMP-140, an inducible granule membrane protein of platelets and endothelium. , 1990 .