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2 - Dicer in RNAi: Its roles in vivo and utility in vitro

Published online by Cambridge University Press:  31 July 2009

By
Jason W. Myers  and
James E. Ferrell Jr.
Edited by
Krishnarao Appasani
Foreword by
Andrew Fire  and
Marshall Nirenberg
Jason W. Myers
Affiliation:
Department of Molecular Pharmacology, Stanford University School of Medicine
James E. Ferrell Jr.
Affiliation:
Department of Molecular Pharmacology, Stanford University School of Medicine
Krishnarao Appasani
Affiliation:
GeneExpression Systems, Inc., Massachusetts
Andrew Fire
Affiliation:
Stanford University, California
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Summary

Introduction

In its infancy, RNA interference (RNAi) was simply an intriguing curiosity; now it has leapt to the forefront of science (Couzin, 2002). The growth spurt of RNAi-related studies has been partly pragmatic – RNAi clearly had the potential to evolve into an incredibly powerful technology for manipulating gene expression in diverse cell types, and to a great extent this potential has been realized. Moreover, as a physiological phenomenon, RNAi represents a fascinating and previously unrecognized level of cellular regulation. RNAi is essential for silencing of heterochromatin (Reinhart and Bartel, 2002; Volpe et al., 2002; Schramke and Allshire, 2003; Volpe et al., 2003) and gene expression via methylation (Grant, 1999; Jones et al., 1999), for antiviral defense, at least in plants (Baulcombe, 1999; Grant, 1999; Ratcliff et al., 1999), for controlling the expression of transposable elements and repetitive sequences (Ketting et al., 1999; Tabara et al., 1999; Ambros et al., 2003a&b; Sijen and Plasterk, 2003), and for proper embryonic development (Grishok et al., 2001; Hütvagner et al., 2001; Ketting et al., 2001; Knight and Bass, 2001; Bernstein et al., 2003; Houbaviy et al., 2003).

This chapter focuses on Dicer, an RNAse III family enzyme essential for sequence-specific gene suppression. We begin with an overview of the discovery of Dicer and its implication in RNAi, followed by a discussion of its hypothesized roles in vivo.

Type
Chapter
Information
RNA Interference Technology
From Basic Science to Drug Development
 , pp. 29 - 54
Publisher: Cambridge University Press
Print publication year: 2005

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References

Abbas-Terki, T., Blanco-Bose, W., Deglon, N., Pralong, W. and Aebischer, P. (2002). Lentiviral-mediated RNA interference. Human Gene Therapy, 13, 2197–2201CrossRefGoogle ScholarPubMed
Ambros, V., Bartel, B., Bartel, D. P., Burge, C. B., Carrington, J. C., Chen, X., Dreyfuss, G., Eddy, S. R., Griffiths-Jones, S., Marshall, M., Matzke, M., Ruvkun, G. and Tuschl, T. (2003a). A uniform system for microRNA annotation. RNA, 9, 277–279CrossRefGoogle Scholar
Ambros, V., Lee, R. C., Lavanway, A., Williams, P. T. and Jewell, D. (2003b). microRNAs and other tiny endogenous RNAs in C. elegans. Current Biology, 13, 807–818CrossRefGoogle Scholar
An, D. S., Xie, Y., Mao, S. H., Morizono, K., Kung, S. K. and Chen, I. S. (2003). Efficient lentiviral vectors for short hairpin RNA delivery into human cells. Human Gene Therapy, 14, 1207–1212CrossRefGoogle ScholarPubMed
Andino, R. (2003). RNAi puts a lid on virus replication. Nature Biotechnology, 21, 629–630CrossRefGoogle ScholarPubMed
Angell, S. M. and Baulcombe, D. C. (1997). Consistent gene silencing in transgenic plants expressing a replicating potato virus X RNA. European Molecular Biology Organization Journal, 16, 3675–3684CrossRefGoogle ScholarPubMed
Arasu, P., Wightman, B. and Ruvkun, G. (1991). Temporal regulation of lin-14 by the antagonistic action of two other heterochronic genes, lin-14 by the antagonistic action of two other heterochronic genes, lin-4 and lin-28. Genes & Development, 5, 1825–1833CrossRefGoogle ScholarPubMed
Aravin, A. A., Naumova, N. M., Tulin, A. V., Vagin, V. V., Rozovsky, Y. M. and Gvozdev, V. A. (2001). Double-stranded RNA-mediated silencing of genomic tandem repeats and transposable elements in the D. melanogaster germline. Current Biology, 11, 1017–1027CrossRefGoogle ScholarPubMed
Ashrafi, K., Chang, F. Y., Watts, J. L., Fraser, A. G., Kamath, R. S., Ahringer, J. and Ruvkun, G. (2003). Genome-wide RNAi analysis of Caenorhabditis elegans fat regulatory genes. Nature, 421, 268–272CrossRefGoogle ScholarPubMed
Bartel, B. and Bartel, D. P. (2003). microRNAs: at the root of plant development?Plant Physiology, 132, 709–717CrossRefGoogle ScholarPubMed
Barton, G. M. and Medzhitov, R. (2002). Retroviral delivery of small interfering RNA into primary cells. Proceedings of the National Academy of Sciences USA, 99, 14943–14945CrossRefGoogle ScholarPubMed
Baulcombe, D. C. (1999). Fast forward genetics based on virus-induced gene silencing. Current Opinion in Plant Biology, 2, 109–113CrossRefGoogle ScholarPubMed
Bernstein, E., Caudy, A. A., Hammond, S. M. and Hannon, G. J. (2001). Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature, 409, 363–366CrossRefGoogle ScholarPubMed
Bernstein, E., Kim, S. Y., Carmell, M. A., Murchison, E. P., Alcorn, H., Li, M. Z., Mills, A. A., Elledge, S. J., Anderson, K. V. and Hannon, G. J. (2003). Dicer is essential for mouse development. Nature Genetics, 35, 215–217CrossRefGoogle ScholarPubMed
Bohula, E. A., Salisbury, A. J., Sohail, M., Playford, M. P., Riedemann, J., Southern, E. M. and Macaulay, V. M. (2003). The efficacy of small interfering RNAs targeted to the type 1 insulin-like growth factor receptor (IGF1R) is influenced by secondary structure in the IGF1R. Journal of Biological Chemistry, 278, 15991–15997CrossRefGoogle ScholarPubMed
Bridge, A. J., Pebernard, S., Ducraux, A., Nicoulaz, A. L. and Iggo, R. (2003). Induction of an interferon response by RNAi vectors in mammalian cells. Nature Genetics, 34, 263–264CrossRefGoogle ScholarPubMed
Brummelkamp, T. R., Bernards, R. and Agami, R. (2002a). Stable suppression of tumorigenicity by virus-mediated RNA interference. Cancer Cell, 2, 243–247CrossRefGoogle Scholar
Brummelkamp, T. R., Bernards, R. and Agami, R. (2002b). A system for stable expression of short interfering RNAs in mammalian cells. Science, 296, 550–553CrossRefGoogle Scholar
Brummelkamp, T. R., Nijman, S. M., Dirac, A. M. and Bernards, R. (2003). Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-kappaB. Nature, 424, 797–801CrossRefGoogle ScholarPubMed
Carthew, R. W. (2001). Gene silencing by double-stranded RNA. Current Opinion in Cell Biology, 13, 244–248CrossRefGoogle ScholarPubMed
Castanotto, D., Li, H. and Rossi, J. J. (2002). Functional siRNA expression from transfected PCR products. RNA, 8, 1454–1460CrossRefGoogle ScholarPubMed
Castle, L. A., Errampalli, D., Atherton, T. L., Franzmann, L. H., Yoon, E. S. and Meinke, D. W. (1993). Genetic and molecular characterization of embryonic mutants identified following seed transformation in Arabidopsis. Molecular and General Genetics, 241, 504–514CrossRefGoogle ScholarPubMed
Chi, J. T., Chang, H. Y., Wang, N. N., Chang, D. S., Dunphy, N. and Brown, P. O. (2003). Genomewide view of gene silencing by small interfering RNAs. Proceedings of the National Academy of Sciences USA, 100, 6343–6346CrossRefGoogle ScholarPubMed
Cogoni, C., Irelan, J. T., Schumacher, M., Schmidhauser, T. J., Selker, E. U. and Macino, G. (1996). Transgene silencing of the al-1 gene in vegetative cells of Neurospora is mediated by a cytoplasmic effector and does not depend on DNA-DNA interactions or DNA methylation. European Molecular Biology Organization Journal, 15, 3153–3163Google ScholarPubMed
Couzin, J. (2002). Breakthrough of the year. Small RNAs make big splash. Science, 298, 2296–2297CrossRefGoogle ScholarPubMed
Dalmay, T., Hamilton, A., Rudd, S., Angell, S. and Baulcombe, D. C. (2000). An RNA-dependent RNA polymerase gene in Arabidopsis is required for posttranscriptional gene silencing mediated by a transgene but not by a virus. Cell, 101, 543–553CrossRefGoogle Scholar
Denli, A. M. and Hannon, G. J. (2003). RNAi: An ever-growing puzzle. Trends in Biochemical Sciences, 28, 196–201CrossRefGoogle ScholarPubMed
Dirac, A. M. and Bernards, R. (2003). Reversal of senescence in mouse fibroblasts through lentiviral suppression of p53. Journal of Biological Chemistry, 278, 11731–11734CrossRefGoogle ScholarPubMed
Doench, J. G., Petersen, C. P. and Sharp, P. A. (2003). siRNAs can function as can function as miRNAs. Genes & Development, 17, 438–442CrossRefGoogle ScholarPubMed
Doi, N., Zenno, S., Ueda, R., Ohki-Hamazaki, H., Ui-Tei, K. and Saigo, K. (2003). Short-interfering-RNA-mediated gene silencing in mammalian cells requires Dicer and eIF2C translation initiation factors. Current Biology, 13, 41–46CrossRefGoogle ScholarPubMed
Dougherty, W. G., Lindbo, J. A., Smith, H. A., Parks, T. D., Swaney, S. and Proebsting, W. M. (1994). RNA-mediatedvirus resistance in transgenic plants: Exploitation of a cellular pathway possibly involved in RNA degradation. Mol Plant Microbe Interact, 7, 544–552CrossRefGoogle ScholarPubMed
Dunn, J. J. (1982). Ribonuclease III. In The Enzymes, P. D. Boyer, ed. (New York, Academic Press), pp. 485–499
Dykxhoorn, D. M., Novina, C. D. and Sharp, P. A. (2003). Killing the messenger: Short RNAs that silence gene expression. Nature Reviews Molecular Cell Biology, 4, 457–467CrossRefGoogle ScholarPubMed
Elbashir, S. M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K. and Tuschl, T. (2001a). Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature, 411, 494–498CrossRefGoogle Scholar
Elbashir, S. M., Lendeckel, W. and Tuschl, T. (2001b). RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes & Development, 15, 188–200CrossRefGoogle Scholar
Elbashir, S. M., Martinez, J., Patkaniowska, A., Lendeckel, W. and Tuschl, T. (2001c). Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate. European Molecular Biology Organization Journal, 20, 6877–6888CrossRefGoogle Scholar
Elbashir, S. M., Harborth, J., Weber, K. and Tuschl, T. (2002). Analysis of gene function in somatic mammalian cells using small interfering RNAs. Methods, 26, 199–213CrossRefGoogle ScholarPubMed
Errampalli, D., Patton, D., Castle, L., Mickelson, L., Hansen, K., Schnall, J., Feldmann, K. and Meinke, D. (1991). Embryonic lethals and T-DNA insertional mutagenesis in Arabidopsis. Plant Cell, 3, 149–157CrossRefGoogle ScholarPubMed
Feinberg, E. H. and Hunter, C. P. (2003). Transport of dsRNA into cells by the transmembrane protein SID-1. Science, 301, 1545–1547CrossRefGoogle ScholarPubMed
Fink, C. C., Bayer, K. U., Myers, J. W., Ferrell, J. E. Jr., Schulman, H. and Meyer, T. (2003). Selective regulation of neurite extension and synapse formation by the beta but not the alpha isoform of CaMKII. Neuron, 39, 283–297CrossRefGoogle Scholar
Finnegan, E. J., Margis, R. and Waterhouse, P. M. (2003). Posttranscriptional gene silencing is not compromised in the Arabidopsis CARPEL FACTORY (DICER-LIKE1) mutant, a homolog of Dicer-1 from DrosophilaCurrent Biology, 13, 236–240CrossRefGoogle Scholar
Fire, A. (1999). RNA-triggered gene silencing. Trends in Genetics, 15, 358–363CrossRefGoogle ScholarPubMed
Fire, A., Albertson, D., Harrison, S. W. and Moerman, D. G. (1991). Production of antisense RNA leads to effective and specific inhibition of gene expression in C. elegans muscle. Development, 113, 503–514Google ScholarPubMed
Fire, A., Xu, S., Montgomery, M. K., Kostas, S. A., Driver, S. E. and Mello, C. C. (1998). Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature, 391, 806–811CrossRefGoogle ScholarPubMed
Gitlin, L., Karelsky, S. and Andino, R. (2002). Short interfering RNA confers intracellular antiviral immunity in human cells. Nature, 418, 430–434CrossRefGoogle ScholarPubMed
Golden, T. A., Schauer, S. E., Lang, J. D., Pien, S., Mushegian, A. R., Grossniklaus, U., Meinke, D. W. and Ray, A. (2002). SHORT INTEGUMENTS1/SUSPENSOR1/CARPEL FACTORY, a Dicer homolog, is a maternal effect gene required for embryo development in Arabidopsis. Plant Physiology, 130, 808–822CrossRefGoogle ScholarPubMed
Gonczy, P., Echeverri, C., Oegema, K., Coulson, A., Jones, S. J., Copley, R. R., Duperon, J., Oegema, J., Brehm, M., Cassin, E., Hannak, E., Kirkham, M., Pichler, S., Flohrs, K., Goessen, A., Leidel, S., Alleaume, A. M., Martin, C., Ozlu, N., Bork, P. and Hyman, A. A. (2000). Functional genomic analysis of cell division in C. elegans using RNAi of genes on chromosome III. Nature, 408, 331–336CrossRefGoogle Scholar
Grant, S. R. (1999). Dissecting the mechanisms of posttranscriptional gene silencing: Divide and conquer. Cell, 96, 303–306CrossRefGoogle ScholarPubMed
Grishok, A. and Mello, C. C. (2002). RNAi (Nematodes: Caenorhabditis elegans). Advances in Genetics, 46, 339–360Google Scholar
Grishok, A., Pasquinelli, A. E., Conte, D., Li, N., Parrish, S., Ha, I., Baillie, D. L., Fire, A., Ruvkun, G. and Mello, C. C. (2001). Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell, 106, 23–34CrossRefGoogle ScholarPubMed
Guo, S. and Kemphues, K. J. (1995). par-1, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed. Cell, 81, 611–620CrossRefGoogle Scholar
Hamilton, A., Voinnet, O., Chappell, L. and Baulcombe, D. (2002). Two classes of short interfering RNA in RNA silencing. European Molecular Biology Organization Journal, 21, 4671–4679CrossRefGoogle ScholarPubMed
Hamilton, A. J. and Baulcombe, D. C. (1999). A species of small antisense RNA in posttranscriptional gene silencing in plants. Science, 286, 950–952CrossRefGoogle ScholarPubMed
Hammond, S. M., Bernstein, E., Beach, D. and Hannon, G. J. (2000). An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. Nature, 404, 293–296CrossRefGoogle ScholarPubMed
Hammond, S. M., Caudy, A. A. and Hannon, G. J. (2001). PostPost-transcriptional gene silencing by double-stranded RNA. Nature Reviews Genetics, 2, 110–119CrossRefGoogle ScholarPubMed
Hannon, G. J. (2002). RNA interference. Nature, 418, 244–251CrossRefGoogle ScholarPubMed
Hemann, M. T., Fridman, J. S., Zilfou, J. T., Hernando, E., Paddison, P. J., Cordon-Cardo, C., Hannon, G. J. and Lowe, S. W. (2003). An epi-allelic series of p53 hypomorphs created by stable RNAi produces distinct tumor phenotypes in vivoNature Genetics, 33, 396–400CrossRefGoogle ScholarPubMed
Houbaviy, H. B., Murray, M. F. and Sharp, P. A. (2003). Embryonic stem cell-specific Micro-RNAs. Developmental Cell, 5, 351–358CrossRefGoogle Scholar
Hunter, C. P. (2000). Gene silencing: shrinking the black box of RNAi. Current Biology, 10, R137–140CrossRefGoogle ScholarPubMed
Hütvagner, G., McLachlan, J., Pasquinelli, A. E., Balint, E., Tuschl, T. and Zamore, P. D. (2001). A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science, 293, 834–838CrossRefGoogle ScholarPubMed
Hütvagner, G. and Zamore, P. D. (2002a). A microRNA in a multiple-turnover RNAi enzyme complex. Science, 297, 2056–2060CrossRefGoogle Scholar
Hütvagner, G. and Zamore, P. D. (2002b). RNAi: Nature abhors a double-strand. Current Opinion in Genetics and Development, 12, 225–232CrossRefGoogle Scholar
Jackson, A. L., Bartz, S. R., Schelter, J., Kobayashi, S. V., Burchard, J., Mao, M., Li, B., Cavet, G. and Linsley, P. S. (2003). Expression profiling reveals off-target gene regulation by RNAi. Nature Biotechnology, 21, 635–637CrossRefGoogle ScholarPubMed
Jacobsen, S. E., Running, M. P. and Meyerowitz, E. M. (1999). Disruption of an RNA helicase/RNase III gene in Arabidopsis causes unregulated cell division in floral meristems. Development, 126, 5231–5243Google ScholarPubMed
Jones, L., Hamilton, A. J., Voinnet, O., Thomas, C. L., Maule, A. J. and Baulcombe, D. C. (1999). RNA-DNA interactions and DNA methylation in post-transcriptional gene silencing. Plant Cell, 11, 2291–2301CrossRefGoogle ScholarPubMed
Jorgensen, R. (1990). Altered gene expression in plants due to trans-interactions between homologous genes. Trends in Biotechnology, 8, 340–344CrossRefGoogle ScholarPubMed
Kamath, R. S. and Ahringer, J. (2003). Genome-wide RNAi screening in Caenorhabditis elegans. Methods, 30, 313–321CrossRefGoogle ScholarPubMed
Kamath, R. S., Fraser, A. G., Dong, Y., Poulin, G., Durbin, R., Gotta, M., Kanapin, A., Bot, N., Moreno, S., Sohrmann, M., Welchman, D. P., Zipperlen, P. and Ahringer, J. (2003). Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature, 421, 231–237CrossRefGoogle Scholar
Kawasaki, H., Suyama, E., Iyo, M. and Taira, K. (2003). siRNAs generated by recombinant human Dicer induce specific and significant but target site-independent gene silencing in human cells. Nucleic Acids Research, 31, 981–987CrossRefGoogle ScholarPubMed
Kennerdell, J. R. and Carthew, R. W. (1998). Use of dsRNA-mediated genetic interference to demonstrate that frizzled and frizzled 2 act in the wingless pathway. Cell, 95, 1017–1026CrossRefGoogle ScholarPubMed
Ketting, R. F., Fischer, S. E., Bernstein, E., Sijen, T., Hannon, G. J. and Plasterk, R. H. (2001). Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans. Genes & Development, 15, 2654–2659CrossRefGoogle ScholarPubMed
Ketting, R. F., Haverkamp, T. H., Luenen, H. G. and Plasterk, R. H. (1999). Mut-7 of C. elegans, required for transposon silencing and RNA interference, is a homolog of Werner syndrome helicase and RNAseD. Cell, 99, 133–141CrossRefGoogle ScholarPubMed
Khvorova, A., Reynolds, A. and Jayasena, S. D. (2003). Functional siRNAs and miRNAs exhibit strand bias. Cell, 115, 209–216CrossRefGoogle ScholarPubMed
Kiger, A., Baum, B., Jones, S., Jones, M., Coulson, A., Echeverri, C. and Perrimon, N. (2003). A functional genomic analysis of cell morphology using RNA interference. Journal of Biology, 2, 27CrossRefGoogle ScholarPubMed
Knight, S. W. and Bass, B. L. (2001). A role for the RNAse III enzyme DCR-1 in RNA interference and germ line development in Caenorhabditis elegans. Science, 293, 2269–2271CrossRefGoogle ScholarPubMed
Kostura, M. and Mathews, M. B. (1989). Purification and activation of the double-stranded RNA-dependent eIF-2 kinase DAI. Molecular and Cellular Biology, 9, 1576–1586CrossRefGoogle ScholarPubMed
Kumagai, M. H., Donson, J., della-Cioppa, G., Harvey, D., Hanley, K. and Grill, L. K. (1995). Cytoplasmic inhibition of carotenoid biosynthesis with virus-derived RNA. Proceedings of the National Academy of Sciences USA, 92, 1679–1683CrossRefGoogle ScholarPubMed
Lang, J. D., Ray, S. and Ray, A. (1994). sin 1, a mutation affecting female fertility in Arabidopsis, interacts with mod 1, its recessive modifier. Genetics, 137, 1101–1110Google Scholar
Lassus, P., Opitz-Araya, X. and Lazebnik, Y. (2002). Requirement for caspase-2 in stress-induced apoptosis before mitochondrial permeabilization. Science, 297, 1352–1354CrossRefGoogle ScholarPubMed
Lassus, P., Rodriguez, J. and Lazebnik, Y. (2002). Confirming specificity of RNAi in mammalian cells. Science's STKE: Signal Transduction Knowledge Environment, 2002, PL13Google ScholarPubMed
Lee, N. S., Dohjima, T., Bauer, G., Li, H., Li, M. J., Ehsani, A., Salvaterra, P. and Rossi, J. (2002a). Expression of small interfering RNAs targeted against HIV-1 rev transcripts in human cells. Nature Biotechnology, 20, 500–505CrossRefGoogle Scholar
Lee, Y., Jeon, K., Lee, J. T., Kim, S. and Kim, V. N. (2002b). microRNA maturation: Stepwise processing and subcellular localization. European Molecular Biology Organization Journal, 21, 4663–4670CrossRefGoogle Scholar
Lee, R. C., Feinbaum, R. L. and Ambros, V. (1993). The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell, 75, 843–854CrossRefGoogle Scholar
Lee, S. S., Lee, R. Y., Fraser, A. G., Kamath, R. S., Ahringer, J. and Ruvkun, G. (2003a). A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity. Nature Genetics, 33, 40–48CrossRefGoogle Scholar
Lee, Y., Ahn, C., Han, J., Choi, H., Kim, J., Yim, J., Lee, J., Provost, P., Radmark, O., Kim, S. and Kim, V. N. (2003b). The nuclear RNAse III Drosha initiates microRNA processing. Nature, 425, 415–419CrossRefGoogle Scholar
Lim, L. P., Glasner, M. E., Yekta, S., Burge, C. B. and Bartel, D. P. (2003). Vertebrate microRNA genes. Science, 299, 1540CrossRefGoogle ScholarPubMed
Lingel, A., Simon, B., Izaurralde, E. and Sattler, M. (2003). Structure and nucleic-acid binding of the Drosophila Argonaute 2 PAZ domain. Nature, 426, 465–469CrossRefGoogle ScholarPubMed
Lingel, A., Simon, B., Izaurralde, E. and Sattler, M. (2004). Nucleic acid 3′-end recognition by the Argonaute2 PAZ domain. Nature, Structural and Molecular Biology, 11, 576–577CrossRefGoogle ScholarPubMed
Llave, C., Kasschau, K. D., Rector, M. A. and Carrington, J. C. (2002a). Endogenous and silencing-associated small RNAs in plants. Plant Cell, 14, 1605–1619CrossRefGoogle Scholar
Llave, C., Xie, Z., Kasschau, K. D. and Carrington, J. C. (2002b). Cleavage of scarecrow-like mRNA targets directed by a class of Arabidopsis miRNA. Science, 297, 2053–2056CrossRefGoogle Scholar
Lum, L., Yao, S., Mozer, B., Rovescalli, A., Kessler, D., Nirenberg, M. and Beachy, P. A. (2003). Identification of hedgehog pathway components by RNAi in Drosophila cultured cells. Science, 299, 2039–2045CrossRefGoogle ScholarPubMed
Lustig, K. D., Stukenberg, P. T., McGarry, T. J., King, R. W., Cryns, V. L., Mead, P. E., Zon, L. I., Yuan, J. and Kirschner, M. W. (1997). Small pool expression screening: Identification of genes involved in cell cycle control, apoptosis, and early development. Methods in Enzymolgy, 283, 83–99CrossRefGoogle ScholarPubMed
Ma, J. B., Ye, K. and Patel, D. J. (2004). Structural basis for overhang-specific small interfering RNA recognition by the PAZ domain. Nature, 429, 318–322CrossRefGoogle ScholarPubMed
Manche, L., Green, S. R., Schmedt, C. and Mathews, M. B. (1992). Interactions between double-stranded RNA regulators and the protein kinase DAI. Molecular and Cellular Biology, 12, 5238–5248CrossRefGoogle ScholarPubMed
Matta, H., Hozayev, B., Tomar, R., Chugh, P. and Chaudhary, P. M. (2003). Use of lenti-viral vectors for delivery of small interfering RNA. Cancer Biology and Therapy, 2, 206–210CrossRefGoogle Scholar
McElver, J., Tzafrir, I., Aux, G., Rogers, R., Ashby, C., Smith, K., Thomas, C., Schetter, A., Zhou, Q., Cushman, M. A., Tossberg, J., Nickle, T., Levin, J. Z., Law, M., Meinke, D. and Patton, D. (2001). Insertional mutagenesis of genes required for seed development in Arabidopsis thaliana. Genetics, 159, 1751–1763Google ScholarPubMed
Mette, M. F., Aufsatz, W., Winden, J., Matzke, M. A. and Matzke, A. J. (2000). Transcriptional silencing and promoter methylation triggered by double-stranded RNA. European Molecular Biology Organization Journal, 19, 5194–5201CrossRefGoogle ScholarPubMed
Minks, M. A., West, D. K., Benvin, S. and Baglioni, C. (1979). Structural requirements of double-stranded RNA for the activation of 2′,5′-oligo(A) polymerase and proteins kinase of interferon-treated HeLa cells. Journal of Biological Chemistry, 254, 10180–10183Google ScholarPubMed
Miyagishi, M. and Taira, K. (2002). U6 promoter-driven siRNAs with four uridine 3′ overhangs efficiently suppress targeted gene expression in mammalian cells. Nature Biotechnology, 20, 497–500CrossRefGoogle ScholarPubMed
Moss, E. G. (2000). Non-coding RNAs: lightning strikes twice. Current Biology, 10, R436–439CrossRefGoogle ScholarPubMed
Myers, J. W., Jones, J. T., Meyer, T. and Ferrell, J. E. Jr. (2003). Recombinant Dicer efficiently converts large dsRNAs into siRNAs suitable for gene silencing. Nature Biotechnology, 21, 324–328CrossRefGoogle ScholarPubMed
Oefner, P. J. (2002). Sequence variation and the biological function of genes: Methodological and biological considerations Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 782, 3–25CrossRefGoogle Scholar
Olsen, P. H. and Ambros, V. (1999). The lin-4 regulatory RNA controls developmental timing in Caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Developmental Biology, 216, 671–680CrossRefGoogle ScholarPubMed
Paddison, P. J., Caudy, A. A., Bernstein, E., Hannon, G. J. and Conklin, D. S. (2002a). Short hairpin RNAs (shRNAs) induce sequence-specific silencing in mammalian cells. Genes & Development, 16, 948–958CrossRefGoogle Scholar
Paddison, P. J., Caudy, A. A. and Hannon, G. J. (2002b). Stable suppression of gene expression by RNAi in mammalian cells. Proceedings of the National Academy of Sciences USA, 99, 1443–1448CrossRefGoogle Scholar
Paddison, P. J. and Hannon, G. J. (2002). RNA interference: The new somatic cell genetics? Cancer Cell, 2, 17–23CrossRefGoogle ScholarPubMed
Papp, I., Mette, M. F., Aufsatz, W., Daxinger, L., Schauer, S. E., Ray, A., Winden, J., Matzke, M. and Matzke, A. J. (2003). Evidence for nuclear processing of plant micro RNA and short interfering RNA precursors. Plant Physiology, 132, 1382–1390CrossRefGoogle ScholarPubMed
Park, W., Li, J., Song, R., Messing, J. and Chen, X. (2002). CARPEL FACTORY, a Dicer homolog, and HEN1, a novel protein, act in microRNA metabolism in Arabidopsis thaliana. Current Biology, 12, 1484–1495CrossRefGoogle ScholarPubMed
Parrish, S., Fleenor, J., Xu, S., Mello, C. and Fire, A. (2000). Functional anatomy of a dsRNA trigger. Differential requirement for the two trigger strands in RNA interference. Molecular Cell, 6, 1077–1087CrossRefGoogle ScholarPubMed
Pasquinelli, A. E. and Ruvkun, G. (2002). Control of developmental timing by microRNAs and their targets. Annual Review of Cell and Developmental Biology, 18, 495–513CrossRefGoogle ScholarPubMed
Paul, C. P., Good, P. D., Winer, I. and Engelke, D. R. (2002). Effective expression of small interfering RNA in human cells. Nature Biotechnology, 20, 505–508CrossRefGoogle ScholarPubMed
Pothof, J., Haaften, G., Thijssen, K., Kamath, R. S., Fraser, A. G., Ahringer, J., Plasterk, R. H. and Tijsterman, M. (2003). Identification of genes that protect the C. elegans genome against mutations by genome-wide RNAi. Genes & Development, 17, 443–448CrossRefGoogle Scholar
Provost, P., Dishart, D., Doucet, J., Frendewey, D., Samuelsson, B. and Radmark, O. (2002a). Ribonuclease activity and RNA binding of recombinant human Dicer. European Molecular Biology Organization Journal, 21, 5864–5874CrossRefGoogle Scholar
Provost, P., Silverstein, R. A., Dishart, D., Walfridsson, J., Djupedal, I., Kniola, B., Wright, A., Samuelsson, B., Radmark, O. and Ekwall, K. (2002b). Dicer is required for chromosome segregation and gene silencing in fission yeast cells. Proceedings of the National Academy of Sciences USA, 99, 16648–16653CrossRefGoogle Scholar
Ratcliff, F. G., MacFarlane, S. A. and Baulcombe, D. C. (1999). Gene silencing without DNA. RNA-mediated cross-protection between viruses. Plant Cell, 11, 1207–1216CrossRefGoogle ScholarPubMed
Ray, A., Lang, J. D., Golden, T. and Ray, S. (1996a). SHORT INTEGUMENT (SIN1), a gene required for ovule development in Arabidopsis, also controls flowering time. Development, 122, 2631–2638Google Scholar
Ray, S., Golden, T. and Ray, A. (1996b). Maternal effects of the short integument mutation on embryo development in Arabidopsis. Developmental Biology, 180, 365–369CrossRefGoogle Scholar
Reinhart, B. J. and Bartel, D. P. (2002a). Small RNAs correspond to centromere heterochromatic repeats. Science, 297, 1831CrossRefGoogle Scholar
Reinhart, B. J., Weinstein, E. G., Rhoades, M. W., Bartel, B. and Bartel, D. P. (2002b). Micro-RNAs in plants. Genes & Development, 16, 1616–1626CrossRefGoogle Scholar
Reynolds, A., Leake, D., Boese, Q., Scaringe, S., Marshall, W. S. and Khvorova, A. (2004). Rational siRNA design for RNA interference. Nature Biotechnology, 22, 326–330CrossRefGoogle ScholarPubMed
Robertson, H. D. and Hunter, T. (1975). Sensitive methods for the detection and characterization of double helical ribonucleic acid. Journal of Biological Chemistry, 250, 418–425Google ScholarPubMed
Robinson-Beers, K., Pruitt, R. E. and Gasser, C. S. (1992). Ovule development in wild-type Arabidopsis and two female-sterile mutants. Plant Cell, 4, 1237–1249CrossRefGoogle ScholarPubMed
Rubinson, D. A., Dillon, C. P., Kwiatkowski, A. V., Sievers, C., Yang, L., Kopinja, J., Rooney, D. L., Ihrig, M. M., McManus, M. T., Gertler, F. B., Scott, M. L. and Parijs, L. (2003). A lentivirus-based system to functionally silence genes in primary mammalian cells, stem cells and transgenic mice by RNA interference. Nature Genetics, 33, 401–406CrossRefGoogle ScholarPubMed
Ruiz, M. T., Voinnet, O. and Baulcombe, D. C. (1998). Initiation and maintenance of virus-induced gene silencing. Plant Cell, 10, 937–946CrossRefGoogle ScholarPubMed
Samuel, C. E. (2001). Antiviral actions of interferons. Clinical Microbiology Reviews, 14, 778–809CrossRefGoogle ScholarPubMed
Schauer, S. E., Jacobsen, S. E., Meinke, D. W. and Ray, A. (2002). DICER-LIKE1: Blind men and elephants in Arabidopsis development. Trends in Plant Sciences, 7, 487–491CrossRefGoogle ScholarPubMed
Scherr, M., Battmer, K., Ganser, A. and Eder, M. (2003). Modulation of gene expression by lentiviral-mediated delivery of small interfering RNA. Cell Cycle, 2, 251–257CrossRefGoogle ScholarPubMed
Schramke, V. and Allshire, R. (2003). Hairpin RNAs and retrotransposon LTRs effect RNAi and chromatin-based gene silencing. Science, 301, 1069–1074CrossRefGoogle ScholarPubMed
Schwarz, D. S., Hütvagner, G., Du, T., Xu, Z., Aronin, N. and Zamore, P. D. (2003). Asymmetry in the assembly of the RNAi enzyme complex. Cell, 115, 199–208CrossRefGoogle ScholarPubMed
Schwarz, D. S., Hütvagner, G., Haley, B. and Zamore, P. D. (2002). Evidence that siRNAs function as guides, not primers, in the Drosophila and human RNAi pathways. Molecular Cell, 10, 537–548CrossRefGoogle Scholar
Semizarov, D., Frost, L., Sarthy, A., Kroeger, P., Halbert, D. N. and Fesik, S. W. (2003). Specificity of short interfering RNA determined through gene expression signatures. Proceedings of the National Academy of Sciences USA, 100, 6347–6352CrossRefGoogle ScholarPubMed
Sharp, P. A. (2001). RNA interference – 2001. Genes & Development, 15, 485–490CrossRefGoogle ScholarPubMed
Shen, C., Buck, A. K., Liu, X., Winkler, M. and Reske, S. N. (2003). Gene silencing by adenovirus-delivered siRNA. Federation of European Biochemical Society Letters, 539, 111–114CrossRefGoogle ScholarPubMed
Sijen, T. and Plasterk, R. H. (2003). Transposon silencing in the Caenorhabditis elegans germ line by natural RNAi. Nature, 426, 310–314CrossRefGoogle ScholarPubMed
Simmer, F., Moorman, C., Linden, A. M., Kuijk, E., Berghe, P. V., Kamath, R., Fraser, A. G., Ahringer, J. and Plasterk, R. H. (2003). Genome-wide RNAi of C. of C. elegans using the hypersensitive rrf-3 strain reveals novel Gene Functions. Public Library of Science Biology, 1, E12Google ScholarPubMed
Sledz, C. A., Holko, M., Veer, M. J., Silverman, R. H. and Williams, B. R. (2003). Activation of the interferon system by short-interfering RNAs. Nature Cell Biology, 5, 834–839CrossRefGoogle ScholarPubMed
Smith, W. C. and Harland, R. M. (1992). Expression cloning of noggin, a new dorsalizing factor localized to the Spemann organizer in Xenopus embryos. Cell, 70, 829–840CrossRefGoogle ScholarPubMed
Song, J. J., Liu, J., Tolia, N. H., Schneiderman, J., Smith, S. K., Martienssen, R. A., Hannon, G. J. and Joshua-Tor, L. (2003). The crystal structure of the Argonaute2 PAZ domain reveals an RNA binding motif in RNAi effector complexes. Nature Structural Biology, 10, 1026–1032CrossRefGoogle ScholarPubMed
Stark, G. R., Kerr, I. M., Williams, B. R., Silverman, R. H. and Schreiber, R. D. (1998). How cells respond to interferons. Annual Review of Biochemistry, 67, 227–264CrossRefGoogle ScholarPubMed
Tabara, H., Sarkissian, M., Kelly, W. G., Fleenor, J., Grishok, A., Timmons, L., Fire, A. and Mello, C. C. (1999). The rde-1 gene, RNA interference, and transposon silencing in C. elegans. Cell, 99, 123–132CrossRefGoogle ScholarPubMed
Tang, G., Reinhart, B. J., Bartel, D. P. and Zamore, P. D. (2003). A biochemical framework for RNA silencing in plants. Genes & Development, 17, 49–63CrossRefGoogle ScholarPubMed
Thoma, C., Hasselblatt, P., Kock, J., Chang, S. F., Hockenjos, B., Will, H., Hentze, M. W., Blum, H. E., Weizsacker, F. and Offensperger, W. B. (2001). Generation of stable mRNA fragments and translation of N-truncated proteins induced by antisense oligodeoxynucleotides. Molecular Cell, 8, 865–872CrossRefGoogle ScholarPubMed
Tijsterman, M., Ketting, R. F. and Plasterk, R. H. (2002). The genetics of RNA silencing. Annual Review of Genetics, 36, 489–519CrossRefGoogle ScholarPubMed
Timmons, L. and Fire, A. (1998). Specific interference by ingested dsRNA. Nature, 395, 854CrossRefGoogle ScholarPubMed
Tomar, R. S., Matta, H. and Chaudhary, P. M. (2003). Use of adeno-associated viral vector for delivery of small interfering RNA. Oncogene, 22, 5712–5715CrossRefGoogle ScholarPubMed
Tuschl, T., Zamore, P. D., Lehmann, R., Bartel, D. P. and Sharp, P. A. (1999). Targeted mRNA degradation by double-stranded RNA in vitro. Genes & Development, 13, 3191–3197CrossRefGoogle ScholarPubMed
Vastenhouw, N. L., Fischer, S. E., Robert, V. J., Thijssen, K. L., Fraser, A. G., Kamath, R. S., Ahringer, J. and Plasterk, R. H. (2003). A genome-wide screen identifies 27 genes involved in transposon silencing in C. elegans. Current Biology, 13, 1311–1316CrossRefGoogle ScholarPubMed
Vaucheret, H., Beclin, C., Elmayan, T., Feuerbach, F., Godon, C., Morel, J. B., Mourrain, P., Palauqui, J. C. and Vernhettes, S. (1998). Transgene-induced gene silencing in plants. Plant Journal, 16, 651–659CrossRefGoogle ScholarPubMed
Vickers, T. A., Koo, S., Bennett, C. F., Crooke, S. T., Dean, N. M. and Baker, B. F. (2003). Efficient reduction of target RNAs by small interfering RNA and RNAse H-dependent antisense agents. A comparative analysis. Journal of Biological Chemistry, 278, 7108–7118CrossRefGoogle ScholarPubMed
Volpe, T., Schramke, V., Hamilton, G. L., White, S. A., Teng, G., Martienssen, R. A. and Allshire, R. C. (2003). RNA interference is required for normal centromere function in fission yeast. Chromosome Research, 11, 137–146CrossRefGoogle ScholarPubMed
Volpe, T. A., Kidner, C., Hall, I. M., Teng, G., Grewal, S. I. and Martienssen, R. A. (2002). Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science, 297, 1833–1837CrossRefGoogle ScholarPubMed
Winston, W. M., Molodowitch, C. and Hunter, C. P. (2002). Systemic RNAi in C. elegans requires the putative transmembrane protein SID-1. Science, 295, 2456–2459CrossRefGoogle Scholar
Yan, K. S., Yan, S., Farooq, A., Han, A., Zeng, L. and Zhou, M. M. (2003). Structure and conserved RNA binding of the PAZ domain. Nature, 426, 468–474CrossRefGoogle ScholarPubMed
Yang, D., Buchholz, F., Huang, Z., Goga, A., Chen, C. Y., Brodsky, F. M. and Bishop, J. M. (2002). Short RNA duplexes produced by hydrolysis with Escherichia coli RNAse III mediate effective RNA interference in mammalian cells. Proceedings of the National Academy of Sciences USA, 99, 9942–9947CrossRefGoogle ScholarPubMed
Yang, D., Lu, H. and Erickson, J. W. (2000). Evidence that processed small dsRNAs may mediate sequence-specific mRNA degradation during RNAi in Drosophila embryos. Current Biology, 10, 1191–1200CrossRefGoogle ScholarPubMed
Yu, J. Y., DeRuiter, S. L. and Turner, D. L. (2002). RNA interference by expression of short-interfering RNAs and hairpin RNAs in mammalian cells. Proceedings of the National Academy of Sciences USA, 99, 6047–6052CrossRefGoogle ScholarPubMed
Zamore, P. D. (2002). Ancient pathways programmed by small RNAs. Science, 296, 1265–1269CrossRefGoogle ScholarPubMed
Zamore, P. D., Tuschl, T., Sharp, P. A. and Bartel, D. P. (2000). RNAi: Double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell, 101, 25–33CrossRefGoogle ScholarPubMed
Zhang, H., Kolb, F. A., Brondani, V., Billy, E. and Filipowicz, W. (2002). Human Dicer preferentially cleaves dsRNAs at their termini without a requirement for ATP. European Molecular Biology Organization Journal, 21, 5875–5885CrossRefGoogle ScholarPubMed
Zhang, H., Kolb, F. A., Jaskiewicz, L., Westhof, E. and Filipowicz, W. (2004). Single processing center models for human Dicer and bacterial RNAse III. Cell, 118, 57–68CrossRefGoogle ScholarPubMed

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