MicroRNAs in heart development.

MicroRNAs (miRNAs) are a class of small noncoding RNAs of ~22nt in length which are involved in the regulation of gene expression at the posttranscriptional level by degrading their target mRNAs and/or inhibiting their translation. Expressed ubiquitously or in a tissue-specific manner, miRNAs are involved in the regulation of many biological processes such as cell proliferation, differentiation, apoptosis, and the maintenance of normal cellular physiology. Many miRNAs are expressed in embryonic, postnatal, and adult hearts. Aberrant expression or genetic deletion of miRNAs is associated with abnormal cardiac cell differentiation, disruption of heart development, and cardiac dysfunction. This chapter will summarize the history, biogenesis, and processing of miRNAs as well as their function in heart development, remodeling, and disease.

[1]  S. Hammond,et al.  An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells , 2000, Nature.

[2]  T. Tuschl,et al.  MicroRNA-24 Regulates Vascularity After Myocardial Infarction , 2011, Circulation.

[3]  M. Siomi,et al.  Slicer function of Drosophila Argonautes and its involvement in RISC formation. , 2005, Genes & development.

[4]  A. Caudy,et al.  Argonaute2, a Link Between Genetic and Biochemical Analyses of RNAi , 2001, Science.

[5]  G. Ruvkun,et al.  Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans , 1993, Cell.

[6]  G. Ruvkun,et al.  Temporal regulation of lin-14 by the antagonistic action of two other heterochronic genes, lin-4 and lin-28. , 1991, Genes & development.

[7]  W. Rottbauer,et al.  MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts , 2008, Nature.

[8]  Ronald H. A. Plasterk,et al.  A genetic link between co-suppression and RNA interference in C. elegans , 2000, Nature.

[9]  K. Czaplinski,et al.  Exportin 5 is a RanGTP-dependent dsRNA-binding protein that mediates nuclear export of pre-miRNAs. , 2004, RNA.

[10]  Harvey F Lodish,et al.  Myogenic factors that regulate expression of muscle-specific microRNAs. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[11]  David P. Bartel,et al.  MicroRNAs: At the Root of Plant Development?1 , 2003, Plant Physiology.

[12]  H. Horvitz,et al.  Heterochronic mutants of the nematode Caenorhabditis elegans. , 1984, Science.

[13]  D. Bouchez,et al.  AGO1 defines a novel locus of Arabidopsis controlling leaf development , 1998, The EMBO journal.

[14]  H. Arnold,et al.  BMP-2 induces ectopic expression of cardiac lineage markers and interferes with somite formation in chicken embryos , 1998, Mechanisms of Development.

[15]  Da-Zhi Wang,et al.  Shox2 is essential for the differentiation of cardiac pacemaker cells by repressing Nkx2-5. , 2009, Developmental biology.

[16]  Caroline E. Burns,et al.  The miR-143-adducin3 pathway is essential for cardiac chamber morphogenesis , 2010, Development.

[17]  A. Moorman,et al.  The transcriptional repressor Tbx3 delineates the developing central conduction system of the heart. , 2004, Cardiovascular research.

[18]  Da-Zhi Wang,et al.  Activation of Cardiac Gene Expression by Myocardin, a Transcriptional Cofactor for Serum Response Factor , 2001, Cell.

[19]  T. Tuschl,et al.  Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. , 2004, Molecular cell.

[20]  T. Yatskievych,et al.  MicroRNA expression during chick embryo development , 2006, Developmental dynamics : an official publication of the American Association of Anatomists.

[21]  L. Miraglia,et al.  Human RNase III Is a 160-kDa Protein Involved in Preribosomal RNA Processing* , 2000, The Journal of Biological Chemistry.

[22]  Maureen A. Sartor,et al.  MicroRNA-320 Is Involved in the Regulation of Cardiac Ischemia/Reperfusion Injury by Targeting Heat-Shock Protein 20 , 2009, Circulation.

[23]  E. Olson,et al.  A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance. , 2009, Developmental cell.

[24]  R. Plasterk,et al.  mut-7 of C. elegans, Required for Transposon Silencing and RNA Interference, Is a Homolog of Werner Syndrome Helicase and RNaseD , 1999, Cell.

[25]  H. Grosshans,et al.  Target-mediated protection of endogenous microRNAs in C. elegans. , 2011, Developmental cell.

[26]  Xiaodong Wang,et al.  Argonaute2 Cleaves the Anti-Guide Strand of siRNA during RISC Activation , 2005, Cell.

[27]  L. Lim,et al.  An Abundant Class of Tiny RNAs with Probable Regulatory Roles in Caenorhabditis elegans , 2001, Science.

[28]  E. Olson,et al.  An intragenic MEF2-dependent enhancer directs muscle-specific expression of microRNAs 1 and 133 , 2007, Proceedings of the National Academy of Sciences.

[29]  B. Reinhart,et al.  Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA , 2000, Nature.

[30]  L Hartley,et al.  Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeo box gene Nkx2-5. , 1995, Genes & Development.

[31]  Raquel P. Ritchie,et al.  MicroRNA-1 regulates smooth muscle cell differentiation by repressing Kruppel-like factor 4. , 2011, Stem cells and development.

[32]  Gene Kim,et al.  Translational Control of FOG-2 Expression in Cardiomyocytes by MicroRNA-130a , 2009, PloS one.

[33]  Jian-Fu Chen,et al.  microRNA-1 and microRNA-206 regulate skeletal muscle satellite cell proliferation and differentiation by repressing Pax7 , 2010, The Journal of cell biology.

[34]  D. Srivastava,et al.  Regulation of cardiac mesodermal and neural crest development by the bHLH transcription factor, dHAND , 1997, Nature Genetics.

[35]  A. V. Grimstone.  Molecular biology of the cell (3rd edn) , 1995 .

[36]  S. Izumo,et al.  Cardiac and extracardiac expression of Csx/Nkx2.5 homeodomain protein. , 1998, Circulation research.

[37]  I. MacRae,et al.  The RNA-induced Silencing Complex: A Versatile Gene-silencing Machine* , 2009, The Journal of Biological Chemistry.

[38]  Andrew Fire,et al.  The rde-1 Gene, RNA Interference, and Transposon Silencing in C. elegans , 1999, Cell.

[39]  A. Fire,et al.  Production of antisense RNA leads to effective and specific inhibition of gene expression in C. elegans muscle. , 1991, Development.

[40]  Jian-Fu Chen,et al.  Expression of microRNAs is dynamically regulated during cardiomyocyte hypertrophy. , 2007, Journal of molecular and cellular cardiology.

[41]  Jeffrey Robbins,et al.  A Calcineurin-Dependent Transcriptional Pathway for Cardiac Hypertrophy , 1998, Cell.

[42]  Shridar Ganesan,et al.  Dicer-deficient mouse embryonic stem cells are defective in differentiation and centromeric silencing. , 2005, Genes & development.

[43]  R. Shiekhattar,et al.  The Microprocessor complex mediates the genesis of microRNAs , 2004, Nature.

[44]  A. Pasquinelli,et al.  A Cellular Function for the RNA-Interference Enzyme Dicer in the Maturation of the let-7 Small Temporal RNA , 2001, Science.

[45]  Jian-Fu Chen,et al.  Loss of MicroRNAs in Neural Crest Leads to Cardiovascular Syndromes Resembling Human Congenital Heart Defects , 2010, Arteriosclerosis, thrombosis, and vascular biology.

[46]  Gary Ruvkun,et al.  The Caenorhabditis elegans heterochronic gene lin-14 encodes a nuclear protein that forms a temporal developmental switch , 1989, Nature.

[47]  J. Cáceres,et al.  Antagonistic role of hnRNP A1 and KSRP in the regulation of Let-7a biogenesis , 2010, Nature Structural &Molecular Biology.

[48]  R. Jorgensen,et al.  Homology-based control of gene expression patterns in transgenic petunia flowers. , 1998, Developmental genetics.

[49]  B. Long,et al.  miR-9 and NFATc3 Regulate Myocardin in Cardiac Hypertrophy* , 2010, The Journal of Biological Chemistry.

[50]  M. Lu,et al.  Wnt/beta-catenin signaling promotes expansion of Isl-1-positive cardiac progenitor cells through regulation of FGF signaling. , 2007, The Journal of clinical investigation.

[51]  K. Kemphues,et al.  par-1, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed , 1995, Cell.

[52]  S. Guil,et al.  The multifunctional RNA-binding protein hnRNP A1 is required for processing of miR-18a , 2007, Nature Structural &Molecular Biology.

[53]  R. Yeh,et al.  MicroRNA regulation of cell lineages in mouse and human embryonic stem cells. , 2008, Cell stem cell.

[54]  Joshua D. Wythe,et al.  A Slit/miR-218/Robo regulatory loop is required during heart tube formation in zebrafish , 2011, Development.

[55]  Bin Tian,et al.  Comparative Analysis of mRNA Isoform Expression in Cardiac Hypertrophy and Development Reveals Multiple Post-Transcriptional Regulatory Modules , 2011, PloS one.

[56]  N. Perrimon,et al.  An endogenous small interfering RNA pathway in Drosophila , 2008, Nature.

[57]  K. Nishii,et al.  Mode and determination of the initial contraction stage in the mouse embryo heart , 2006, Anatomy and Embryology.

[58]  Robert J. Moore,et al.  A microRNA catalog of the developing chicken embryo identified by a deep sequencing approach. , 2008, Genome research.

[59]  Xiaodong Wang,et al.  R2D2, a Bridge Between the Initiation and Effector Steps of the Drosophila RNAi Pathway , 2003, Science.

[60]  A. Bateman,et al.  Domains in gene silencing and cell differentiation proteins: the novel PAZ domain and redefinition of the Piwi domain. , 2000, Trends in biochemical sciences.

[61]  X. Zhu,et al.  Combined BMP-2 and FGF-4, but neither factor alone, induces cardiogenesis in non-precardiac embryonic mesoderm. , 1996, Developmental biology.

[62]  G. Macino,et al.  Transcription: Gene silencing in worms and fungi , 2000, Nature.

[63]  A. Caudy,et al.  Role for a bidentate ribonuclease in the initiation step of RNA interference , 2001 .

[64]  N. Grishin,et al.  C3PO, an Endoribonuclease That Promotes RNAi by Facilitating RISC Activation , 2009, Science.

[65]  Richard A. Jorgensen,et al.  Chalcone synthase cosuppression phenotypes in petunia flowers: comparison of sense vs. antisense constructs and single-copy vs. complex T-DNA sequences , 1996, Plant Molecular Biology.

[66]  Michael Kyba,et al.  Mesp1 acts as a master regulator of multipotent cardiovascular progenitor specification. , 2008, Cell stem cell.

[67]  K. Jiao,et al.  Ectopic expression of Nkx2.5 suppresses the formation of the sinoatrial node in mice. , 2011, Developmental biology.

[68]  K. Yutzey,et al.  T‐box genes and heart development: Putting the “T” in heart , 2005, Developmental dynamics : an official publication of the American Association of Anatomists.

[69]  B. Bruneau,et al.  The Homeodomain Transcription Factor Irx5 Establishes the Mouse Cardiac Ventricular Repolarization Gradient , 2005, Cell.

[70]  S. Lowe,et al.  A microRNA polycistron as a potential human oncogene , 2005, Nature.

[71]  M. Goumans,et al.  MicroRNA-23 Restricts Cardiac Valve Formation by Inhibiting Has2 and Extracellular Hyaluronic Acid Production , 2011, Circulation research.

[72]  Takeo Matsumoto,et al.  Heartbeat regulates cardiogenesis by suppressing retinoic acid signaling via expression of miR-143 , 2011, Mechanisms of Development.

[73]  Yong Zhao,et al.  Serum response factor regulates a muscle-specific microRNA that targets Hand2 during cardiogenesis , 2005, Nature.

[74]  V. Kim,et al.  The nuclear RNase III Drosha initiates microRNA processing , 2003, Nature.

[75]  Peifeng Li.  MicroRNAs in Cardiac Apoptosis , 2010, Journal of cardiovascular translational research.

[76]  Qiang Sun,et al.  Cardiomyocyte overexpression of miR-27b induces cardiac hypertrophy and dysfunction in mice , 2011, Cell Research.

[77]  Rudolf Jaenisch,et al.  DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal , 2007, Nature Genetics.

[78]  Y. Pinto,et al.  Conditional Dicer Gene Deletion in the Postnatal Myocardium Provokes Spontaneous Cardiac Remodeling , 2008, Circulation.

[79]  C. E. Challice,et al.  The architectural development of the early mammalian heart. , 1974, Tissue & cell.

[80]  G. Dorn,et al.  miR-15 Family Regulates Postnatal Mitotic Arrest of Cardiomyocytes , 2011, Circulation research.

[81]  Yunqing Shi,et al.  Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart. , 2003, Developmental cell.

[82]  M. Abdellatif.  The role of microRNA-133 in cardiac hypertrophy uncovered. , 2010, Circulation research.

[83]  W. Rottbauer,et al.  Targeted Mutation Reveals Essential Functions of the Homeodomain Transcription Factor Shox2 in Sinoatrial and Pacemaking Development , 2007, Circulation.

[84]  A. Fire,et al.  Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans , 1998, Nature.

[85]  Chunxiang Zhang,et al.  MicroRNA Expression Signature and the Role of MicroRNA-21 in the Early Phase of Acute Myocardial Infarction* , 2009, The Journal of Biological Chemistry.

[86]  Dinender K. Singla,et al.  MicroRNA-1 transfected embryonic stem cells enhance cardiac myocyte differentiation and inhibit apoptosis by modulating the PTEN/Akt pathway in the infarcted heart. , 2011, American journal of physiology. Heart and circulatory physiology.

[87]  C. Reggiani,et al.  Thyroid hormone regulation of MHC isoform composition and myofibrillar ATPase activity in rat skeletal muscles. , 1998, Archives of physiology and biochemistry.

[88]  Xi-Long Zheng,et al.  MicroRNA‐1 inhibits myocardin‐induced contractility of human vascular smooth muscle cells , 2010, Journal of cellular physiology.

[89]  Michael T. McManus,et al.  Dysregulation of Cardiogenesis, Cardiac Conduction, and Cell Cycle in Mice Lacking miRNA-1-2 , 2007, Cell.

[90]  E. Olson,et al.  microRNA-133a regulates cardiomyocyte proliferation and suppresses smooth muscle gene expression in the heart. , 2008, Genes & development.

[91]  C. Joo,et al.  TUT4 in Concert with Lin28 Suppresses MicroRNA Biogenesis through Pre-MicroRNA Uridylation , 2009, Cell.

[92]  U. Kutay,et al.  Nuclear Export of MicroRNA Precursors , 2004, Science.

[93]  G. Hannon,et al.  Processing of primary microRNAs by the Microprocessor complex , 2004, Nature.

[94]  David P. Bartel,et al.  Passenger-Strand Cleavage Facilitates Assembly of siRNA into Ago2-Containing RNAi Enzyme Complexes , 2005, Cell.

[95]  H. Seitz,et al.  Structural determinants of miRNAs for RISC loading and slicer-independent unwinding , 2009, Nature Structural &Molecular Biology.

[96]  J. Nerbonne,et al.  MicroRNA-133a Protects Against Myocardial Fibrosis and Modulates Electrical Repolarization Without Affecting Hypertrophy in Pressure-Overloaded Adult Hearts , 2010, Circulation research.

[97]  H. Horvitz,et al.  The lin-14 locus of Caenorhabditis elegans controls the time of expression of specific postembryonic developmental events. , 1987, Genes & development.

[98]  C. Croce,et al.  MicroRNA-133 controls cardiac hypertrophy , 2007, Nature Medicine.

[99]  Joshua D. Wythe,et al.  Tinman/Nkx2-5 acts via miR-1 and upstream of Cdc42 to regulate heart function across species , 2011, The Journal of cell biology.

[100]  U. Kutay,et al.  Exportin‐5‐mediated nuclear export of eukaryotic elongation factor 1A and tRNA , 2002, The EMBO journal.

[101]  C. Semple,et al.  Posttranscriptional Regulation of miRNAs Harboring Conserved Terminal Loops , 2008, Molecular cell.

[102]  V. Ambros,et al.  Mesodermally expressed Drosophila microRNA-1 is regulated by Twist and is required in muscles during larval growth. , 2005, Genes & development.

[103]  Byoung-Tak Zhang,et al.  Molecular Basis for the Recognition of Primary microRNAs by the Drosha-DGCR8 Complex , 2006, Cell.

[104]  S. Chavali,et al.  Cis-regulation of microRNA expression by scaffold/matrix-attachment regions , 2011, Nucleic acids research.

[105]  Danish Sayed,et al.  MicroRNAs in development and disease. , 2011, Physiological reviews.

[106]  T. Tuschl,et al.  Identification of Novel Genes Coding for Small Expressed RNAs , 2001, Science.

[107]  D. Bartel.  MicroRNAs Genomics, Biogenesis, Mechanism, and Function , 2004, Cell.

[108]  E. Sontheimer,et al.  Distinct Roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA Silencing Pathways , 2004, Cell.

[109]  T. Tuschl,et al.  Identification of Tissue-Specific MicroRNAs from Mouse , 2002, Current Biology.

[110]  M. Rosenfeld,et al.  β-Catenin directly regulates Islet1 expression in cardiovascular progenitors and is required for multiple aspects of cardiogenesis , 2007, Proceedings of the National Academy of Sciences.

[111]  Xiaoxia Qi,et al.  Control of Stress-Dependent Cardiac Growth and Gene Expression by a MicroRNA , 2007, Science.

[112]  Danish Sayed,et al.  MicroRNAs Play an Essential Role in the Development of Cardiac Hypertrophy , 2007, Circulation research.

[113]  B. Reinhart,et al.  The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans , 2000, Nature.

[114]  Jiang Chang,et al.  NFATc4 is negatively regulated in miR-133a-mediated cardiomyocyte hypertrophic repression. , 2010, American journal of physiology. Heart and circulatory physiology.

[115]  Zhe Han,et al.  MicroRNA1 influences cardiac differentiation in Drosophila and regulates Notch signaling. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[116]  Da-Zhi Wang,et al.  MicroRNAs in Cardiac Remodeling and Disease , 2010, Journal of cardiovascular translational research.

[117]  D. Bartel.  MicroRNAs: Target Recognition and Regulatory Functions , 2009, Cell.

[118]  R. Harvey.  Organogenesis: Patterning the vertebrate heart , 2002, Nature Reviews Genetics.

[119]  E. Yamashita,et al.  Selective nuclear export mechanism of small RNAs. , 2011, Current opinion in structural biology.

[120]  Amy A. Caudy,et al.  Post-transcriptional gene silencing by double-stranded RNA , 2001, Nature Reviews Genetics.

[121]  G. Stoecklin,et al.  On track with P-bodies. , 2010, Biochemical Society transactions.

[122]  D. Bartel,et al.  Intronic microRNA precursors that bypass Drosha processing , 2007, Nature.

[123]  Yi Liu,et al.  QIP, a putative exonuclease, interacts with the Neurospora Argonaute protein and facilitates conversion of duplex siRNA into single strands. , 2007, Genes & development.

[124]  A. Moorman,et al.  Cooperative action of Tbx2 and Nkx2.5 inhibits ANF expression in the atrioventricular canal: implications for cardiac chamber formation. , 2002, Genes & development.

[125]  V. Ambros,et al.  The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 , 1993, Cell.

[126]  Martin Chalfie,et al.  Mutations that lead to reiterations in the cell lineages of C. elegans , 1981, Cell.

[127]  M. Kühl,et al.  The role of Wnt signalling in cardiac development and tissue remodelling in the mature heart. , 2006, Cardiovascular research.

[128]  Y. Jan,et al.  A new homeobox-containing gene, msh-2, is transiently expressed early during mesoderm formation of Drosophila. , 1990, Development.

[129]  L. Leinwand,et al.  The mammalian myosin heavy chain gene family. , 1996, Annual review of cell and developmental biology.

[130]  S. Izumo,et al.  The cardiac homeobox gene Csx/Nkx2.5 lies genetically upstream of multiple genes essential for heart development. , 1999, Development.

[131]  M. Brilliant,et al.  Sox6 regulation of cardiac myocyte development. , 2003, Nucleic acids research.

[132]  E. Olson,et al.  Gene Regulatory Networks in the Evolution and Development of the Heart , 2006, Science.

[133]  Jitendra P Khurana,et al.  Genome-wide identification, organization and phylogenetic analysis of Dicer-like, Argonaute and RNA-dependent RNA Polymerase gene families and their expression analysis during reproductive development and stress in rice , 2008, BMC Genomics.

[134]  Ryozo Nagai,et al.  Tbx5 associates with Nkx2-5 and synergistically promotes cardiomyocyte differentiation , 2001, Nature Genetics.

[135]  Stefan L Ameres,et al.  Cleavage of the siRNA passenger strand during RISC assembly in human cells , 2006, EMBO reports.

[136]  Björn Olsson,et al.  Expression of microRNAs and their target mRNAs in human stem cell-derived cardiomyocyte clusters and in heart tissue. , 2011, Physiological genomics.

[137]  J. Rossant,et al.  FGF signaling regulates mesoderm cell fate specification and morphogenetic movement at the primitive streak. , 2001, Developmental cell.

[138]  B. Williams,et al.  PKR; a sentinel kinase for cellular stress , 1999, Oncogene.

[139]  P. Krieg,et al.  tinman-related genes expressed during heart development in Xenopus. , 1998, Developmental genetics.

[140]  Michael D. Schneider,et al.  Targeted deletion of Dicer in the heart leads to dilated cardiomyopathy and heart failure , 2008, Proceedings of the National Academy of Sciences.

[141]  T. Tuschl,et al.  New microRNAs from mouse and human. , 2003, RNA.

[142]  Jian-Fu Chen,et al.  The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation , 2006, Nature Genetics.

[143]  Marie-José Goumans,et al.  MicroRNA-1 and -499 Regulate Differentiation and Proliferation in Human-Derived Cardiomyocyte Progenitor Cells , 2010, Arteriosclerosis, thrombosis, and vascular biology.

[144]  S. Elledge,et al.  Dicer is essential for mouse development , 2003, Nature Genetics.

[145]  S. Kauppinen,et al.  Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice. , 2010, The Journal of clinical investigation.

[146]  A. Pasquinelli,et al.  Genes and Mechanisms Related to RNA Interference Regulate Expression of the Small Temporal RNAs that Control C. elegans Developmental Timing , 2001, Cell.

[147]  You-yi Zhang,et al.  miR‐1/miR‐206 regulate Hsp60 expression contributing to glucose‐mediated apoptosis in cardiomyocytes , 2010, FEBS letters.

[148]  M. Buckingham,et al.  Building the mammalian heart from two sources of myocardial cells , 2005, Nature Reviews Genetics.

[149]  D. Srivastava,et al.  microRNA-138 modulates cardiac patterning during embryonic development , 2008, Proceedings of the National Academy of Sciences.

[150]  W. Blankesteijn,et al.  The Wnt/frizzled pathway in cardiovascular development and disease: friend or foe? , 2008, European journal of pharmacology.

[151]  V. Ambros,et al.  An Extensive Class of Small RNAs in Caenorhabditis elegans , 2001, Science.

[152]  J. Miyazaki,et al.  MesP1 is expressed in the heart precursor cells and required for the formation of a single heart tube. , 1999, Development.

[153]  Da-Zhi Wang,et al.  Myocardin Induces Cardiomyocyte Hypertrophy , 2006, Circulation research.

[154]  H. Vaucheret,et al.  AGO1, QDE-2, and RDE-1 are related proteins required for post-transcriptional gene silencing in plants, quelling in fungi, and RNA interference in animals. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[155]  Rudolf Jaenisch,et al.  Targeted Deletion Reveals Essential and Overlapping Functions of the miR-17∼92 Family of miRNA Clusters , 2008, Cell.

[156]  R. Shiekhattar,et al.  TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing , 2005, Nature.

[157]  Jian Wang,et al.  Transforming growth factor-β-regulated miR-24 promotes skeletal muscle differentiation , 2008, Nucleic acids research.

[158]  Da-Zhi Wang,et al.  Induction of MicroRNA-1 by Myocardin in Smooth Muscle Cells Inhibits Cell Proliferation , 2011, Arteriosclerosis, thrombosis, and vascular biology.

[159]  Jian-Fu Chen,et al.  MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice. , 2009, The Journal of clinical investigation.

[160]  D. Catalucci,et al.  Reciprocal Regulation of MicroRNA-1 and Insulin-Like Growth Factor-1 Signal Transduction Cascade in Cardiac and Skeletal Muscle in Physiological and Pathological Conditions , 2009, Circulation.

[161]  C. Goodman,et al.  Slit Is the Midline Repellent for the Robo Receptor in Drosophila , 1999, Cell.

[162]  I. Gessner,et al.  The morphologic development of the sinoatrial node in the mouse. , 1970, The American journal of cardiology.

[163]  D. Srivastava.  Making or Breaking the Heart: From Lineage Determination to Morphogenesis , 2006, Cell.

[164]  E. Tzahor,et al.  Wnt/β-Catenin Signaling and Cardiogenesis: Timing Does Matter , 2007 .

[165]  Thomas Thum,et al.  MicroRNAs in the Human Heart: A Clue to Fetal Gene Reprogramming in Heart Failure , 2007 .

[166]  C. Tabin,et al.  miRNA-processing enzyme Dicer is necessary for cardiac outflow tract alignment and chamber septation , 2009, Proceedings of the National Academy of Sciences.

[167]  Y. Saga,et al.  MesP1 and MesP2 are essential for the development of cardiac mesoderm. , 2000, Development.

[168]  D. Srivastava,et al.  MicroRNA regulation of cardiovascular development. , 2009, Circulation research.

[169]  B. Cullen,et al.  Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. , 2003, Genes & development.