The growing catalog of small RNAs and their association with distinct Argonaute/Piwi family members

Several distinct classes of small RNAs, some newly identified, have been discovered to play important regulatory roles in diverse cellular processes. These classes include siRNAs, miRNAs, rasiRNAs and piRNAs. Each class binds to distinct members of the Argonaute/Piwi protein family to form ribonucleoprotein complexes that recognize partially, or nearly perfect, complementary nucleic acid targets, and that mediate a variety of regulatory processes, including transcriptional and post-transcriptional gene silencing. Based on the known relationship of Argonaute/Piwi proteins with distinct classes of small RNAs, we can now predict how many new classes of small RNAs or silencing processes remain to be discovered.

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

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

[3]  M. Gorovsky,et al.  Conjugation-specific small RNAs in Tetrahymena have predicted properties of scan (scn) RNAs involved in genome rearrangement. , 2004, Genes & development.

[4]  Jef D. Boeke,et al.  Mighty Piwis Defend the Germline against Genome Intruders , 2007, Cell.

[5]  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.

[6]  Doron Betel,et al.  Computational Analysis of Mouse piRNA Sequence and Biogenesis , 2007, PLoS Comput. Biol..

[7]  N. Rajewsky.  microRNA target predictions in animals , 2006, Nature Genetics.

[8]  R. E. Webster,et al.  A nuclease specific for double-stranded RNA. , 1967, Virology.

[9]  D. Marks,et al.  The small RNA profile during Drosophila melanogaster development. , 2003, Developmental cell.

[10]  D. Barford,et al.  Structural insights into mRNA recognition from a PIWI domain–siRNA guide complex , 2005, Nature.

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

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

[13]  Peter F Stadler,et al.  Molecular evolution of a microRNA cluster. , 2004, Journal of molecular biology.

[14]  Leemor Joshua-Tor,et al.  Slicer and the argonautes. , 2007, Nature chemical biology.

[15]  H. Vaucheret.  Post-transcriptional small RNA pathways in plants: mechanisms and regulations. , 2006, Genes & development.

[16]  S. Gygi,et al.  Two different Argonaute complexes are required for siRNA generation and heterochromatin assembly in fission yeast , 2007, Nature Structural &Molecular Biology.

[17]  T. Kai,et al.  Unique germ-line organelle, nuage, functions to repress selfish genetic elements in Drosophila melanogaster , 2007, Proceedings of the National Academy of Sciences.

[18]  Phillip D. Zamore,et al.  Ribo-gnome: The Big World of Small RNAs , 2005, Science.

[19]  T. Rana,et al.  Translation Repression in Human Cells by MicroRNA-Induced Gene Silencing Requires RCK/p54 , 2006, PLoS biology.

[20]  W. Filipowicz,et al.  Repression of protein synthesis by miRNAs: how many mechanisms? , 2007, Trends in cell biology.

[21]  Chris Sander,et al.  The developmental miRNA profiles of zebrafish as determined by small RNA cloning. , 2005, Genes & development.

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

[23]  G. Hutvagner,et al.  A microRNA in a Multiple-Turnover RNAi Enzyme Complex , 2002, Science.

[24]  S. Pfeffer,et al.  Viruses, microRNAs and cancer , 2006, Oncogene.

[25]  N. Rajewsky,et al.  Cell-type-specific signatures of microRNAs on target mRNA expression. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

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

[27]  E. Ullu,et al.  Function of the Trypanosome Argonaute 1 Protein in RNA Interference Requires the N-terminal RGG Domain and Arginine 735 in the Piwi Domain* , 2004, Journal of Biological Chemistry.

[28]  T. Du,et al.  RISC Assembly Defects in the Drosophila RNAi Mutant armitage , 2004, Cell.

[29]  Min Han,et al.  GW182 family proteins are crucial for microRNA-mediated gene silencing. , 2007, Trends in cell biology.

[30]  Kuniaki Saito,et al.  Gene silencing mechanisms mediated by Aubergine piRNA complexes in Drosophila male gonad. , 2007, RNA.

[31]  Thomas Tuschl,et al.  siRNAs: applications in functional genomics and potential as therapeutics , 2004, Nature Reviews Drug Discovery.

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

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

[34]  Xiaofeng Cao,et al.  ARGONAUTE4 Control of Locus-Specific siRNA Accumulation and DNA and Histone Methylation , 2003, Science.

[35]  B. Reinhart,et al.  Small RNAs Correspond to Centromere Heterochromatic Repeats , 2002, Science.

[36]  A. Djikeng,et al.  RNA interference in Trypanosoma brucei: cloning of small interfering RNAs provides evidence for retroposon-derived 24-26-nucleotide RNAs. , 2001, RNA.

[37]  M. Hentze,et al.  A conserved motif in Argonaute-interacting proteins mediates functional interactions through the Argonaute PIWI domain , 2007, Nature Structural &Molecular Biology.

[38]  M. Nowacki,et al.  Nowa1p and Nowa2p: Novel Putative RNA Binding Proteins Involved in trans-Nuclear Crosstalk in Paramecium tetraurelia , 2005, Current Biology.

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

[40]  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.

[41]  G. Hannon,et al.  Control of translation and mRNA degradation by miRNAs and siRNAs. , 2006, Genes & development.

[42]  T. Schüpbach,et al.  zucchini and squash encode two putative nucleases required for rasiRNA production in the Drosophila germline. , 2007, Developmental cell.

[43]  Yunje Cho,et al.  Crystal structure of human DGCR8 core , 2007, Nature Structural &Molecular Biology.

[44]  O. Borsani,et al.  Endogenous siRNAs Derived from a Pair of Natural cis-Antisense Transcripts Regulate Salt Tolerance in Arabidopsis , 2005, Cell.

[45]  Kaleb M. Pauley,et al.  The role of GW/P-bodies in RNA processing and silencing , 2007, Journal of Cell Science.

[46]  G. Macino,et al.  Involvement of small RNAs and role of the qde genes in the gene silencing pathway in Neurospora. , 2002, Genes & development.

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

[48]  V. Kim,et al.  MicroRNA precursors in motion: exportin-5 mediates their nuclear export. , 2004, Trends in cell biology.

[49]  G. Hannon,et al.  A complex system of small RNAs in the unicellular green alga Chlamydomonas reinhardtii. , 2007, Genes & development.

[50]  Pamela J. Green,et al.  Role of RNA polymerase IV in plant small RNA metabolism , 2007, Proceedings of the National Academy of Sciences.

[51]  Julius Brennecke,et al.  Identification of Drosophila MicroRNA Targets , 2003, PLoS biology.

[52]  Thomas Tuschl,et al.  RISC is a 5' phosphomonoester-producing RNA endonuclease. , 2004, Genes & development.

[53]  R. Rauhut,et al.  Ribonuclease III: new sense from nuisance. , 2002, The international journal of biochemistry & cell biology.

[54]  T. Tuschl,et al.  Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells , 2001, Nature.

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

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

[57]  Xianwu Zheng,et al.  Role of Arabidopsis AGO6 in siRNA accumulation, DNA methylation and transcriptional gene silencing , 2007, The EMBO journal.

[58]  S. Akira,et al.  Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2 , 2007, Proceedings of the National Academy of Sciences.

[59]  V. Ambros,et al.  MicroRNAs and Other Tiny Endogenous RNAs in C. elegans , 2003, Current Biology.

[60]  Franck Vazquez,et al.  The action of ARGONAUTE1 in the miRNA pathway and its regulation by the miRNA pathway are crucial for plant development. , 2004, Genes & development.

[61]  M. Manoharan,et al.  RNAi therapeutics: a potential new class of pharmaceutical drugs , 2006, Nature chemical biology.

[62]  D. Baulcombe,et al.  SDE3 encodes an RNA helicase required for post‐transcriptional gene silencing in Arabidopsis , 2001, The EMBO journal.

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

[64]  Robert A. Martienssen,et al.  Noncoding RNAs and Gene Silencing , 2007, Cell.

[65]  Franck Vazquez,et al.  Arabidopsis endogenous small RNAs: highways and byways. , 2006, Trends in plant science.

[66]  S. Grewal,et al.  Heterochromatin revisited , 2007, Nature Reviews Genetics.

[67]  Yijun Qi,et al.  Biochemical specialization within Arabidopsis RNA silencing pathways. , 2005, Molecular cell.

[68]  D. Barford,et al.  Argonaute: A scaffold for the function of short regulatory RNAs. , 2006, Trends in biochemical sciences.

[69]  E. Ullu,et al.  Selection and Characterization of RNA Interference-Deficient Trypanosomes Impaired in Target mRNA Degradation , 2004, Eukaryotic Cell.

[70]  T. Tuschl,et al.  Structural biology of RNA silencing and its functional implications. , 2006, Cold Spring Harbor symposia on quantitative biology.

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

[72]  G. Hannon,et al.  MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline. , 2007, Developmental cell.

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

[74]  M. Wassenegger,et al.  Nomenclature and functions of RNA-directed RNA polymerases. , 2006, Trends in plant science.

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

[76]  Haifan Lin,et al.  MIWI associates with translational machinery and PIWI-interacting RNAs (piRNAs) in regulating spermatogenesis , 2006, Proceedings of the National Academy of Sciences.

[77]  Roy Parker,et al.  P bodies and the control of mRNA translation and degradation. , 2007, Molecular cell.

[78]  M. Carmell,et al.  Posttranscriptional Gene Silencing in Plants , 2006 .

[79]  H. Nakayashiki.  RNA silencing in fungi: Mechanisms and applications , 2005, FEBS letters.

[80]  Anton J. Enright,et al.  Identification of Virus-Encoded MicroRNAs , 2004, Science.

[81]  W. Theurkauf,et al.  Drosophila rasiRNA pathway mutations disrupt embryonic axis specification through activation of an ATR/Chk2 DNA damage response. , 2007, Developmental cell.

[82]  Haifan Lin,et al.  A novel class of small RNAs in mouse spermatogenic cells. , 2006, Genes & development.

[83]  C. Burge,et al.  The microRNAs of Caenorhabditis elegans. , 2003, Genes & development.

[84]  Angela N. Brooks,et al.  Structural Basis for Double-Stranded RNA Processing by Dicer , 2006, Science.

[85]  P. Zamore,et al.  ATP Requirements and Small Interfering RNA Structure in the RNA Interference Pathway , 2001, Cell.

[86]  D. Baulcombe,et al.  Arabidopsis ARGONAUTE1 is an RNA Slicer that selectively recruits microRNAs and short interfering RNAs. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[87]  W. Theurkauf,et al.  Biogenesis and germline functions of piRNAs , 2007, Development.

[88]  Mihaela Zavolan,et al.  Inference of miRNA targets using evolutionary conservation and pathway analysis , 2007, BMC Bioinformatics.

[89]  Akira Ishizuka,et al.  Distinct roles for Argonaute proteins in small RNA-directed RNA cleavage pathways. , 2004, Genes & development.

[90]  N. Perrimon,et al.  High-throughput RNAi screening in cultured cells: a user's guide , 2006, Nature Reviews Genetics.

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

[92]  Xuemei Chen,et al.  Methylation Protects miRNAs and siRNAs from a 3′-End Uridylation Activity in Arabidopsis , 2005, Current Biology.

[93]  Gunter Meister,et al.  Argonaute proteins: mediators of RNA silencing. , 2007, Molecular cell.

[94]  L. Lerman,et al.  Small RNA. , 1983, Science.

[95]  H. L. Sänger,et al.  RNA-directed RNA polymerase from tomato leaves. II. Catalytic in vitro properties. , 1993, The Journal of biological chemistry.

[96]  C. Burge,et al.  Prediction of Mammalian MicroRNA Targets , 2003, Cell.

[97]  Olivier Voinnet,et al.  Induction and suppression of RNA silencing: insights from viral infections , 2005, Nature Reviews Genetics.

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

[99]  Xuemei Chen,et al.  Methylation as a Crucial Step in Plant microRNA Biogenesis , 2005, Science.

[100]  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.

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

[102]  T. Tuschl,et al.  Identification of Novel Argonaute-Associated Proteins , 2005, Current Biology.

[103]  Henning Urlaub,et al.  Single-Stranded Antisense siRNAs Guide Target RNA Cleavage in RNAi , 2002, Cell.

[104]  T. Tuschl,et al.  RNA interference is mediated by 21- and 22-nucleotide RNAs. , 2001, Genes & development.

[105]  Ji-Joon Song,et al.  Purified Argonaute2 and an siRNA form recombinant human RISC , 2005, Nature Structural &Molecular Biology.

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

[107]  Colin N. Dewey,et al.  A Genome-Wide Map of Conserved MicroRNA Targets in C. elegans , 2006, Current Biology.

[108]  V. Kim,et al.  MicroRNA maturation: stepwise processing and subcellular localization , 2002, The EMBO journal.

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

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

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

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

[113]  Phillip D Zamore,et al.  microPrimer: the biogenesis and function of microRNA , 2005, Development.

[114]  R. Russell,et al.  Animal MicroRNAs Confer Robustness to Gene Expression and Have a Significant Impact on 3′UTR Evolution , 2005, Cell.

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

[116]  Sean D. Taverna,et al.  Methylation of Histone H3 at Lysine 9 Targets Programmed DNA Elimination in Tetrahymena , 2002, Cell.

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

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

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

[120]  P. Sharp,et al.  RNAi Double-Stranded RNA Directs the ATP-Dependent Cleavage of mRNA at 21 to 23 Nucleotide Intervals , 2000, Cell.

[121]  Phillip D Zamore,et al.  Beginning to understand microRNA function , 2007, Cell Research.

[122]  Eugene Berezikov,et al.  Mammalian mirtron genes. , 2007, Molecular cell.

[123]  H. Ebhardt,et al.  Extensive 3' modification of plant small RNAs is modulated by helper component-proteinase expression. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

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

[125]  Thomas Tuschl,et al.  Structural basis for 5′-end-specific recognition of guide RNA by the A. fulgidus Piwi protein , 2005, Nature.

[126]  Yifan Liu,et al.  Histone H3 lysine 9 methylation is required for DNA elimination in developing macronuclei in Tetrahymena. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[127]  E. Chan,et al.  Small interfering RNA-mediated silencing induces target-dependent assembly of GW/P bodies. , 2007, Molecular biology of the cell.

[128]  J. Kitzman,et al.  Determinants of targeting by endogenous and exogenous microRNAs and siRNAs. , 2007, RNA.

[129]  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.

[130]  K. Collins,et al.  Two classes of endogenous small RNAs in Tetrahymena thermophila. , 2006, Genes & development.

[131]  Phillip D. Zamore,et al.  Drosophila microRNAs Are Sorted into Functionally Distinct Argonaute Complexes after Production by Dicer-1 , 2007, Cell.

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

[133]  J. Carrington,et al.  Regulation of AUXIN RESPONSE FACTOR3 by TAS3 ta-siRNA Affects Developmental Timing and Patterning in Arabidopsis , 2006, Current Biology.

[134]  M. Kiriakidou,et al.  An mRNA m7G Cap Binding-like Motif within Human Ago2 Represses Translation , 2007, Cell.

[135]  M. Mann,et al.  miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs. , 2002, Genes & development.

[136]  Nicolas Bouché,et al.  DRB4-Dependent TAS3 trans-Acting siRNAs Control Leaf Morphology through AGO7 , 2006, Current Biology.

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

[138]  Xiaofeng Cao,et al.  Role of Arabidopsis ARGONAUTE4 in RNA-Directed DNA Methylation Triggered by Inverted Repeats , 2004, Current Biology.

[139]  Zissimos Mourelatos,et al.  An mRNA m 7 G Cap Binding-like Motif withinHumanAgo2RepressesTranslation , 2007 .

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

[141]  Phillip D Zamore,et al.  Evidence that siRNAs function as guides, not primers, in the Drosophila and human RNAi pathways. , 2002, Molecular cell.

[142]  HEN1 recognizes 21–24 nt small RNA duplexes and deposits a methyl group onto the 2′ OH of the 3′ terminal nucleotide , 2006, Nucleic acids research.

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

[144]  Jing Wu,et al.  The Drosophila SDE3 Homolog armitage Is Required for oskar mRNA Silencing and Embryonic Axis Specification , 2004, Cell.

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

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

[147]  M. Zavolan,et al.  Strand-specific 5'-O-methylation of siRNA duplexes controls guide strand selection and targeting specificity. , 2007, RNA.

[148]  A. Djikeng,et al.  Argonaute Protein in the Early Divergent Eukaryote Trypanosoma brucei: Control of Small Interfering RNA Accumulation and Retroposon Transcript Abundance , 2004, Molecular and Cellular Biology.

[149]  J. Kelly,et al.  ARGONAUTE4 Control of Locus-Specific siRNA Accumulation and DNA and Histone Methylation , 2003 .

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

[151]  I. MacRae,et al.  Ribonuclease revisited: structural insights into ribonuclease III family enzymes. , 2007, Current opinion in structural biology.

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

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

[154]  N. Tolia,et al.  Argonaute Slicing Is Required for Heterochromatic Silencing and Spreading , 2006, Science.

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

[156]  Zissimos Mourelatos,et al.  The mouse homolog of HEN1 is a potential methylase for Piwi-interacting RNAs. , 2007, RNA.

[157]  D. Bartel,et al.  MicroRNAS and their regulatory roles in plants. , 2006, Annual review of plant biology.

[158]  John F. G. Atack,et al.  RNA Interference , 2010, Methods in Molecular Biology.

[159]  D. Sahagian,et al.  El Niño Events Recorded by Stalagmite Carbon Isotopes , 2002, Science.

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

[161]  L. Lim,et al.  Widespread siRNA "off-target" transcript silencing mediated by seed region sequence complementarity. , 2006, RNA.

[162]  D. Patel,et al.  Structural basis for overhang-specific small interfering RNA recognition by the PAZ domain , 2004, Nature.

[163]  Gang Wu,et al.  Trans-acting siRNA-mediated repression of ETTIN and ARF4 regulates heteroblasty in Arabidopsis , 2006, Development.

[164]  B. Li,et al.  Expression profiling reveals off-target gene regulation by RNAi , 2003, Nature Biotechnology.

[165]  D. Baulcombe,et al.  miRNAs control gene expression in the single-cell alga Chlamydomonas reinhardtii , 2007, Nature.

[166]  N. Lau,et al.  The coming of age for Piwi proteins. , 2007, Molecular cell.

[167]  H. L. Sänger,et al.  RNA-directed RNA polymerase from tomato leaves. I. Purification and physical properties. , 1993, The Journal of biological chemistry.

[168]  G. Rubin,et al.  Computational identification of Drosophila microRNA genes , 2003, Genome Biology.

[169]  Andrew G Fraser,et al.  Genome-Wide RNAi of C. elegans Using the Hypersensitive rrf-3 Strain Reveals Novel Gene Functions , 2003, PLoS biology.

[170]  L. Lim,et al.  MicroRNA targeting specificity in mammals: determinants beyond seed pairing. , 2007, Molecular cell.