The Discovery of Rna Interference (rnai) Biogenesis of Small Rnas on the Road to Reading the Rna-interference Code Insight Review

The finding that sequence-specific gene silencing occurs in response to the presence of double-stranded RNAs has had an enormous impact on biology, uncovering an unsuspected level of regulation of gene expression. This process, known as RNA interference (RNAi) or RNA silencing, involves small non-coding RNAs, which associate with nuclease-containing regulatory complexes and then pair with complementary messenger RNA targets, thereby preventing the expression of these mRNAs. Remarkable progress has been made towards understanding the underlying mechanisms of RNAi, raising the prospect of deciphering the 'RNAi code' that, like transcription factors, allows the fine-tuning and networking of complex suites of gene activity, thereby specifying cellular physiology and development.

[1]  L. Joshua-Tor,et al.  Argonautes confront new small RNAs. , 2007, Current opinion in chemical biology.

[2]  Steven P. Gygi,et al.  RNAi-Dependent and -Independent RNA Turnover Mechanisms Contribute to Heterochromatic Gene Silencing , 2007, Cell.

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

[4]  Kuniaki Saito,et al.  Specific association of Piwi with rasiRNAs derived from retrotransposon and heterochromatic regions in the Drosophila genome. , 2006, Genes & development.

[5]  Ravi Sachidanandam,et al.  A germline-specific class of small RNAs binds mammalian Piwi proteins , 2006, Nature.

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

[7]  E. Mardis.  The impact of next-generation sequencing technology on genetics. , 2008, Trends in genetics : TIG.

[8]  Manolis Kellis,et al.  Discrete Small RNA-Generating Loci as Master Regulators of Transposon Activity in Drosophila , 2007, Cell.

[9]  William Stafford Noble,et al.  Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project , 2007, Nature.

[10]  M. Gorovsky,et al.  A Dicer-like protein in Tetrahymena has distinct functions in genome rearrangement, chromosome segregation, and meiotic prophase. , 2005, Genes & development.

[11]  Phillip D. Zamore,et al.  Sorting of Drosophila Small Silencing RNAs , 2007, Cell.

[12]  Christopher M. Player,et al.  Large-Scale Sequencing Reveals 21U-RNAs and Additional MicroRNAs and Endogenous siRNAs in C. elegans , 2006, Cell.

[13]  N. Lau,et al.  Characterization of the piRNA Complex from Rat Testes , 2006, Science.

[14]  Kuniaki Saito,et al.  Pimet, the Drosophila homolog of HEN1, mediates 2'-O-methylation of Piwi- interacting RNAs at their 3' ends. , 2007, Genes & development.

[15]  岡村 勝友.  Distinct roles for Argonaute proteins in small RNA-directed RNA cleavage pathways , 2004 .

[16]  Andrew Fire,et al.  Distinct Populations of Primary and Secondary Effectors During RNAi in C. elegans , 2007, Science.

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

[18]  G. Daley,et al.  Selective Blockade of MicroRNA Processing by Lin28 , 2008, Science.

[19]  Ryan D. Morin,et al.  Application of massively parallel sequencing to microRNA profiling and discovery in human embryonic stem cells. , 2008, Genome research.

[20]  L. Smirnova,et al.  A feedback loop comprising lin-28 and let-7 controls pre-let-7 maturation during neural stem-cell commitment , 2008, Nature Cell Biology.

[21]  Peng Wang,et al.  The Drosophila RNA Methyltransferase, DmHen1, Modifies Germline piRNAs and Single-Stranded siRNAs in RISC , 2007, Current Biology.

[22]  M. Siomi,et al.  Characterization of endogenous human Argonautes and their miRNA partners in RNA silencing. , 2008, Nucleic acids symposium series.

[23]  G. Dreyfuss,et al.  Messenger-RNA-binding proteins and the messages they carry , 2002, Nature Reviews Molecular Cell Biology.

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

[25]  E. Lai,et al.  The Mirtron Pathway Generates microRNA-Class Regulatory RNAs in Drosophila , 2007, Cell.

[26]  Toshiaki Watanabe,et al.  Identification and characterization of two novel classes of small RNAs in the mouse germline: retrotransposon-derived siRNAs in oocytes and germline small RNAs in testes. , 2006, Genes & development.

[27]  R. Russell,et al.  Principles of MicroRNA–Target Recognition , 2005, PLoS biology.

[28]  Phillip D Zamore,et al.  Perspective: machines for RNAi. , 2005, Genes & development.

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

[30]  Z. Weng,et al.  Endogenous siRNAs Derived from Transposons and mRNAs in Drosophila Somatic Cells , 2008, Science.

[31]  Kuniaki Saito,et al.  A Slicer-Mediated Mechanism for Repeat-Associated siRNA 5' End Formation in Drosophila , 2007, Science.

[32]  Anastasia Khvorova,et al.  Functional siRNAs and miRNAs Exhibit Strand Bias , 2003, Cell.

[33]  B. Cullen,et al.  Recognition and cleavage of primary microRNA precursors by the nuclear processing enzyme Drosha , 2005, The EMBO journal.

[34]  V. Kim.  MicroRNA biogenesis: coordinated cropping and dicing , 2005, Nature Reviews Molecular Cell Biology.

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

[36]  Pedro J. Batista,et al.  Analysis of the C. elegans Argonaute Family Reveals that Distinct Argonautes Act Sequentially during RNAi , 2006, Cell.

[37]  G. Hannon,et al.  Crystal Structure of Argonaute and Its Implications for RISC Slicer Activity , 2004, Science.

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

[39]  Eugene Berezikov,et al.  Piwi and piRNAs act upstream of an endogenous siRNA pathway to suppress Tc3 transposon mobility in the Caenorhabditis elegans germline. , 2008, Molecular cell.

[40]  P. Zamore,et al.  A Protein Sensor for siRNA Asymmetry , 2004, Science.

[41]  F. Slack,et al.  Small non-coding RNAs in animal development , 2008, Nature Reviews Molecular Cell Biology.

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

[43]  James C. Carrington,et al.  Specialization and evolution of endogenous small RNA pathways , 2007, Nature Reviews Genetics.

[44]  Oliver H. Tam,et al.  Pseudogene-derived small interfering RNAs regulate gene expression in mouse oocytes , 2008, Nature.

[45]  Qinghua Liu,et al.  Dicer-2 and R2D2 coordinately bind siRNA to promote assembly of the siRISC complexes. , 2006, RNA.

[46]  Zissimos Mourelatos,et al.  Mouse Piwi-interacting RNAs are 2′-O-methylated at their 3′ termini , 2007, Nature Structural &Molecular Biology.

[47]  James C. Carrington,et al.  Specificity of ARGONAUTE7-miR390 Interaction and Dual Functionality in TAS3 Trans-Acting siRNA Formation , 2008, Cell.

[48]  Eugene Berezikov,et al.  A Role for Piwi and piRNAs in Germ Cell Maintenance and Transposon Silencing in Zebrafish , 2007, Cell.

[49]  C. Sander,et al.  A Mammalian microRNA Expression Atlas Based on Small RNA Library Sequencing , 2007, Cell.

[50]  J. M. Thomson,et al.  Argonaute2 Is the Catalytic Engine of Mammalian RNAi , 2004, Science.

[51]  T. Tuschl,et al.  Mechanisms of gene silencing by double-stranded RNA , 2004, Nature.

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

[53]  P. Zamore,et al.  Kinetic analysis of the RNAi enzyme complex , 2004, Nature Structural &Molecular Biology.

[54]  Javier Martinez,et al.  The human RNA kinase hClp1 is active on 3′ transfer RNA exons and short interfering RNAs , 2007, Nature.

[55]  G. Hannon,et al.  Conserved themes in small-RNA-mediated transposon control. , 2008, Trends in cell biology.

[56]  A. Denli,et al.  Normal microRNA Maturation and Germ-Line Stem Cell Maintenance Requires Loquacious, a Double-Stranded RNA-Binding Domain Protein , 2005, PLoS biology.

[57]  Y. Sakaki,et al.  Endogenous siRNAs from naturally formed dsRNAs regulate transcripts in mouse oocytes , 2008, Nature.

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

[59]  Kuniaki Saito,et al.  Processing of Pre-microRNAs by the Dicer-1–Loquacious Complex in Drosophila Cells , 2005, PLoS biology.

[60]  Erik J Sontheimer,et al.  Molecular Requirements for RNA-induced Silencing Complex Assembly in the Drosophila RNA Interference Pathway* , 2005, Journal of Biological Chemistry.

[61]  S. Peltz,et al.  Identification of a Human Endonuclease Complex Reveals a Link between tRNA Splicing and Pre-mRNA 3′ End Formation , 2004, Cell.

[62]  R. Shiekhattar,et al.  Human RISC Couples MicroRNA Biogenesis and Posttranscriptional Gene Silencing , 2005, Cell.

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

[64]  Vladimir Gvozdev,et al.  A Distinct Small RNA Pathway Silences Selfish Genetic Elements in the Germline , 2006, Science.

[65]  Martin J. Simard,et al.  Argonaute proteins: key players in RNA silencing , 2008, Nature Reviews Molecular Cell Biology.

[66]  D. Bartel,et al.  The Drosophila hairpin RNA pathway generates endogenous short interfering RNAs , 2008, Nature.

[67]  Titia Sijen,et al.  Secondary siRNAs Result from Unprimed RNA Synthesis and Form a Distinct Class , 2007, Science.

[68]  M. Todesco,et al.  Target mimicry provides a new mechanism for regulation of microRNA activity , 2007, Nature Genetics.

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

[70]  T. Tuschl,et al.  Structure of the guide-strand-containing argonaute silencing complex , 2008, Nature.

[71]  Eric Westhof,et al.  Single Processing Center Models for Human Dicer and Bacterial RNase III , 2004, Cell.

[72]  Ravi Sachidanandam,et al.  Developmentally Regulated piRNA Clusters Implicate MILI in Transposon Control , 2007, Science.

[73]  Thomas Tuschl,et al.  The growing catalog of small RNAs and their association with distinct Argonaute/Piwi family members , 2008, Development.

[74]  E. Izaurralde,et al.  P bodies: at the crossroads of post-transcriptional pathways , 2007, Nature Reviews Molecular Cell Biology.

[75]  K. Okawa,et al.  In vitro analyses of the production and activity of secondary small interfering RNAs in C. elegans , 2007, The EMBO journal.

[76]  O. Hobert.  Common logic of transcription factor and microRNA action. , 2004, Trends in biochemical sciences.

[77]  Reuven Agami,et al.  RNA-Binding Protein Dnd1 Inhibits MicroRNA Access to Target mRNA , 2007, Cell.

[78]  C. Burge,et al.  Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA Targets , 2005, Cell.

[79]  A. Hata,et al.  SMAD proteins control DROSHA-mediated microRNA maturation , 2008, Nature.

[80]  Haifan Lin,et al.  An epigenetic activation role of Piwi and a Piwi-associated piRNA in Drosophila melanogaster , 2007, Nature.

[81]  J. Nakayama,et al.  Conserved Ribonuclease, Eri1, Negatively Regulates Heterochromatin Assembly in Fission Yeast , 2006, Current Biology.

[82]  Gary Ruvkun,et al.  A conserved siRNA-degrading RNase negatively regulates RNA interference in C. elegans , 2004, Nature.

[83]  C. Sander,et al.  A novel class of small RNAs bind to MILI protein in mouse testes , 2006, Nature.

[84]  Olivier Voinnet,et al.  Antiviral Immunity Directed by Small RNAs , 2007, Cell.

[85]  Gregory J. Hannon,et al.  Sorting of Small RNAs into Arabidopsis Argonaute Complexes Is Directed by the 5′ Terminal Nucleotide , 2008, Cell.

[86]  T. Du,et al.  Asymmetry in the Assembly of the RNAi Enzyme Complex , 2003, Cell.

[87]  M. Hentze,et al.  3′ end mRNA processing: molecular mechanisms and implications for health and disease , 2008, The EMBO journal.

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

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

[90]  I. MacRae,et al.  Structural determinants of RNA recognition and cleavage by Dicer , 2007, Nature Structural &Molecular Biology.

[91]  V. Vance,et al.  Small RNAs in viral infection and host defense. , 2008, Trends in plant science.

[92]  Tariq M Rana,et al.  RNA helicase A interacts with RISC in human cells and functions in RISC loading. , 2007, Molecular cell.

[93]  Stefan L Ameres,et al.  Molecular Basis for Target RNA Recognition and Cleavage by Human RISC , 2007, Cell.

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

[95]  Z. Mourelatos,et al.  A human, ATP-independent, RISC assembly machine fueled by pre-miRNA. , 2005, Genes & development.

[96]  Philip C. J. Donoghue,et al.  MicroRNAs and the advent of vertebrate morphological complexity , 2008, Proceedings of the National Academy of Sciences.

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

[98]  Pedro J. Batista,et al.  PRG-1 and 21U-RNAs interact to form the piRNA complex required for fertility in C. elegans. , 2008, Molecular cell.

[99]  Taishin Kin,et al.  Drosophila endogenous small RNAs bind to Argonaute 2 in somatic cells , 2008, Nature.

[100]  H. Ueda,et al.  The 3′ termini of mouse Piwi-interacting RNAs are 2′-O-methylated , 2007, Nature Structural &Molecular Biology.