Genes required for RNA interference

doi:10.1017/CBO9780511546402.006

3 - Genes required for RNA interference

Published online by Cambridge University Press: 31 July 2009

Nathaniel R. Dudley ,

Ahmad Z. Amin and

Bob Goldstein

Edited by

Krishnarao Appasani

Foreword by

Andrew Fire and

Marshall Nirenberg

Show author details

Nathaniel R. Dudley: Affiliation:
Biology Department, University of North Carolina
Ahmad Z. Amin: Affiliation:
Biology Department, University of North Carolina
Bob Goldstein: Affiliation:
Biology Department, University of North Carolina
Krishnarao Appasani: Affiliation:
GeneExpression Systems, Inc., Massachusetts
Andrew Fire: Affiliation:
Stanford University, California

Book contents

Get access

Summary

Introduction

RNA interference (RNAi) is a recently discovered phenomenon in which double-stranded RNA (dsRNA) silences endogenous gene expression in a sequence-specific manner (Fire et al., 1998). Since its discovery, the use of RNAi has become widely employed in many organisms to specifically knock down gene function. RNAi shares a remarkable degree of similarity with silencing phenomena in other organisms (Cogoni et al., 1999a; Sharp, 1999). For instance, RNAi, post-transcriptional gene silencing in plants and cosuppression in fungi can all be activated by the presence of aberrant RNAs (Maine, 2000; Tijsterman et al., 2002a). Additionally, plant, worm, and fly cells or extracts undergoing RNA-mediated interference all contain small dsRNAs, around 25 nucleotides in length, identical to the sequences present in the silenced gene (Baulcombe, 1996; Hammond et al., 2000; Zamore et al., 2000; Catalanotto et al., 2000).

The high degree of similarity between these RNA-mediated silencing phenomena supports the notion that they were derived from an ancient and conserved pathway used to regulate gene expression, presumably to eliminate defective RNAs and to defend against viral infections and transposons (Zamore, 2002). Components of RNAi have also been implicated in developmental processes, suggesting that RNAi may play a broader role in regulating gene expression (Smardon et al., 2000; Knight et al., 2001; et al., Ketting et al., 2001).

Although we have learned much about the general mechanisms underlying RNAi, a detailed understanding of how RNAi works remains to be elucidated.

Information

Type: Chapter
Information: RNA Interference Technology
From Basic Science to Drug Development
, pp. 55 - 68

DOI: https://doi.org/10.1017/CBO9780511546402.006 [Opens in a new window]

Publisher: Cambridge University Press

Print publication year: 2005

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Book purchase

Temporarily unavailable

References

Alder, M. N., Dames, S., Gaudet, J., and Mango, S. E. (2003). Gene silencing in Caenorhabditis elegans by transitive RNA interference. RNA, 9, 25–32CrossRef Google Scholar PubMed

Bateman, A. (2002). The SGS3 protein involved in PTGS finds a family. BMC Bioinformatics, 3, 21CrossRef Google Scholar PubMed

Baulcombe, D. C. (1996). RNA as a target and an initiator of post-transcriptional gene silencing in transgenic plants. Plant Molecular Biology, 32, 79–88CrossRef Google Scholar PubMed

Boutet, S., Vazquez, F., Liu, J., Beclin, C., Fagard, M., Gratias, A., Morel, J. B., Crete, P., Chen, X., and Vaucheret, H., (2003). Arabidopsis HEN1. A Genetic link between endogenous miRNA controlling development and siRNA controlling transgene silencing and virus resistance. Current Biology, 13, 843–848CrossRef Google Scholar PubMed

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, 363–366CrossRef Google Scholar PubMed

Cao, R., Wang, L., Wang, H., Xia, L., Erdjument-Bromage, H., Tempst, P., Jones, R. S. and Zhang, Y., (2002). Role of histone H3 lysine 27 methylation in polycomb-group silencing. Science, 298, 1039–1043CrossRef Google Scholar PubMed

Carrington, J. C. and Ambros, V., (2003). Role of microRNAs in plant and animal development. Science, 301, 336–338CrossRef Google Scholar PubMed

Catalanotto, C., Azzalin, G., Macino, G., and Cogoni, C., (2000). Gene silencing in worms and fungi. Nature, 404, 245CrossRef Google Scholar PubMed

Caudy, A. A., Myers, M., Hannon, G. J. and Hammond, S. M. (2002). Fragile X-related protein and VIG associate with the RNA interference machinery. Genes & Development, 16, 2491–2496CrossRef Google Scholar PubMed

Caudy, A. A., Ketting, R. F., Hammond, S. M., Denli, A. M., Bathoorn, A. M., Tops, B. B., Silva, J. M., Myers, M. M., Hannon, G. J. and Plasterk, R. H. (2003). A micrococcal nuclease homologue in RNAi effector complexes. Nature, 425, 411–414CrossRef Google Scholar PubMed

Celotto, A. M. and Graveley, B. R. (2002). Exon-specific RNAi: a tool for dissecting the functional relevance of alternative splicing. RNA, 8, 718–724CrossRef Google Scholar PubMed

Cogoni, C. and Macino, G., (1999a). Homology-dependent gene silencing in plants and fungi: A number of variations on the same theme. Current Opinion in Microbiology, 2, 657–662CrossRef Google Scholar

Cogoni, C. and Macino, G., (1999b). Posttranscriptional gene silencing in Neurospora by a RecQ DNA helicase. Science, 286, 2342–2344CrossRef Google Scholar

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, 543–553CrossRef Google Scholar

Dalmay, T., Horsefield, R., Braunstein, T. H. and Baulcombe, D. C. (2001). SDE3 encodes an RNA helicase required for post-transcriptional gene silencing in Arabidopsis. European Molecular Biology Organization Journal, 20, 2069–2078CrossRef Google Scholar PubMed

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, 41–46CrossRef Google Scholar PubMed

Domeier, M. E., Morse, D. P., Knight, S. W., Portereiko, M., Bass, B. L. and Mango, S. E. (2000). A link between RNA interference and nonsense-mediated decay in Caenorhabditis elegans. Science, 289, 1928–1931CrossRef Google Scholar PubMed

Dudley, N. R., Labbe, J. C. and Goldstein, B., (2002). Using RNA interference to identify genes required for RNA interference. Proceedings of the National Academy of Sciences USA, 99, 4191–4196CrossRef Google Scholar PubMed

Elbashir, S. M., Lendeckel, W., and Tuschl, T., (2001a). RNA interference is mediated by 21- and 22-nucleotide RNAs. Genes & Development, 15, 188–200CrossRef Google Scholar

Elbashir, S. M., Martinez, J., Patkaniowska, A., Lendeckel, W., and Tuschl, T., (2001b). Functional anatomy of siRNAs for mediating efficient RNAi in Drosophila melanogaster embryo lysate. European Molecular Biology Organization Journal, 20, 6877–6888CrossRef Google Scholar

Elbashir, S. M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K., and Tuschl, T., (2001c). Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature, 411, 494–498CrossRef Google Scholar

Fagard, M., Boutet, S., Morel, J. B., Bellini, C., and Vaucheret, H., (2000). 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. Proceedings of the National Academy of Sciences USA, 97, 11650–11654CrossRef Google Scholar PubMed

Feinberg, E. H. and Hunter, C. P. (2003). Transport of dsRNA into cells by the transmembrane protein SID-1. Science, 301, 1545–1547CrossRef Google Scholar PubMed

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, 806–811CrossRef Google Scholar PubMed

Glazov, E., Phillips, K., Budziszewski, G. J., Meins, F., and Levin, J. Z. (2003). A gene encoding an RNAse D exonuclease-like protein is required for post-transcriptional silencing in Arabidopsis. Plant Journal, 35, 342–349CrossRef Google Scholar PubMed

Grewal, S. I. and Klar, A. J. (1996). Chromosomal inheritance of epigenetic states in fission yeast during mitosis and meiosis. Cell, 86, 95–101CrossRef Google Scholar PubMed

Grishok, A., Tabara, H., and Mello, C. C. (2000). Genetic requirements for inheritance of RNAi in C. elegans. Science, 287, 2494–2497CrossRef Google Scholar PubMed

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, 23–34CrossRef Google Scholar PubMed

Hall, I. M., Shankaranarayana, G. D., Noma, K., Ayoub, N., Cohen, A., and Grewal, S. I. (2002). Establishment and maintenance of a heterochromatin domain. Science, 297, 2232–2237CrossRef Google Scholar PubMed

Hall, I. M., Noma, K., and Grewal, S. I. (2003). RNA interference machinery regulates chromosome dynamics during mitosis and meiosis in fission yeast. Proceedings of the National Academy of Sciences USA, 100, 193–198CrossRef Google Scholar PubMed

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, 293–296CrossRef Google Scholar PubMed

Hammond, S. M., Boettcher, S., Caudy, A. A., Kobayashi, R., and Hannon, G. J. (2001). Argonaute2, a link between genetic and biochemical analyses of RNAi. Science, 293, 1146–1150CrossRef Google Scholar PubMed

Heaton, J. H., Dlakic, W. M., Dlakic, M., and Gelehrter, T. D. (2001). Identification and cDNA cloning of a novel RNA-binding protein that interacts with the cyclic nucleotide-responsive sequence in the Type-1 plasminogen activator inhibitor mRNA. Journal of Biological Chemistry, 276, 3341–3347CrossRef Google Scholar PubMed

Holen, T., Amarzguioui, M., Wiiger, M. T., Babaie, E., and Prydz, H., (2002). Positional effects of short interfering RNAs targeting the human coagulation trigger Tissue Factor. Nucleic Acids Research, 30, 1757–1766CrossRef Google Scholar PubMed

Hunter, C. P. (1999). Genetics: A touch of elegance with RNAi. Current Biology, 9, R440–R422CrossRef Google Scholar PubMed

Hütvagner, G. and Zamore, P. D. (2002). A microRNA in a multiple-turnover RNAi enzyme complex. Science, 297, 2056–2060CrossRef Google Scholar

Ishizuka, A., Siomi, M. C. and Siomi, H., (2002). A Drosophila Fragile X protein interacts with components of RNAi and ribosomal proteins. Genes & Development, 16, 2497–2508CrossRef Google Scholar PubMed

Kayne, P. S., Kim, U. J., Han, M., Mullen, J. R., Yoshizaki, F., and Grunstein, M., (1988). Extremely conserved histone H4 N terminus is dispensable for growth but essential for repressing the silent mating loci in yeast. Cell, 55, 27–39CrossRef Google Scholar

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, 1017–1026CrossRef Google Scholar PubMed

Kennerdell, J. R., Yamaguchi, S., and Carthew, R. W. (2002). RNAi is activated during Drosophila oocyte maturation in a manner dependent on aubergine and spindle-E. Genes & Development, 16, 1884–1889CrossRef Google Scholar

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, 133–141CrossRef Google Scholar PubMed

Ketting, R. F. and Plasterk, R. H. (2000). A genetic link between co-suppression and RNA interference in C. elegans. Nature, 404, 296–298CrossRef Google Scholar PubMed

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, 2654–2659CrossRef Google Scholar PubMed

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, 2269–2271CrossRef Google Scholar PubMed

Lipardi, C., Wei, Q., and Paterson, B. M. (2001). RNAi as random degradative PCR: siRNA primers convert mRNA into dsRNAs that are degraded to generate new siRNAs. Cell, 107, 297–307CrossRef Google Scholar PubMed

Liu, Q., Rand, T. A., Kalidas, S., Du, F., Kim, H. E., Smith, D. P. and Wang, X., (2003). R2D2, a bridge between the initiation and effector steps of the Drosophila RNAi pathway. Science, 301, 1921–1925CrossRef Google Scholar PubMed

Maine, E. M. (2000). A conserved mechanism for post-transcriptional gene silencing?Genome Biology, 1, REVIEWS1018CrossRef Google Scholar PubMed

Martens, H., Novotny, J., Oberstrass, J., Steck, T. L., Postlethwait, P., and Nellen, W., (2002). RNAi in Dictyostelium: The role of RNA-directed RNA polymerases and double-stranded RNAse. Molecular Biology Cell, 13, 445–453CrossRef Google Scholar PubMed

Morel, J. B., Mourrain, P., Beclin, C., and Vaucheret, H., (2000). DNA methylation and chromatin structure affect transcriptional and post-transcriptional transgene silencing in Arabidopsis. Current Biology, 10, 1591–1594CrossRef Google Scholar PubMed

Mourrain, P., Beclin, C., Elmayan, T., Feuerbach, F., Godon, C., Morel, J. B., Jouette, D., Lacombe, A. M., Nikic, S., Picault, N., Remoue, K., Sanial, M., Vo, T. A. and Vaucheret, H., (2000). Arabidopsis SGS2 and SGS3 genes are required for posttranscriptional gene silencing and natural virus resistance. Cell, 101, 533–542CrossRef Google Scholar PubMed

Nykanen, A., Haley, B., and Zamore, P. D. (2001). ATP requirements and small interfering RNA structure in the RNA interference pathway. Cell, 107, 309–321CrossRef Google Scholar PubMed

Pal-Bhadra, M., Bhadra, U., and Birchler, J. A. (2002). RNAi related mechanisms affect both transcriptional and posttranscriptional transgene silencing in Drosophila. Molecular Cell, 9, 315–327CrossRef Google Scholar PubMed

Palauqui, J. C., Elmayan, T., Pollien, J. M. and Vaucheret, H., (1997). Systemic acquired silencing: Transgene-specific post-transcriptional silencing is transmitted by grafting from silenced stocks to non-silenced scions. European Molecular Biology Organization Journal, 16, 4738–4745CrossRef Google Scholar PubMed

Parrish, S., and Fire, A. (2001). Distinct roles for RDE-1 and RDE-4 during RNA interference in Caenorhabditis elegans. RNA, 7, 1397–1402Google Scholar PubMed

Pirrotta, V. (2002). Silence in the germ. Cell, 110, 661–664CrossRef Google Scholar PubMed

Roignant, J. Y., Carre, C., Mugat, B., Szymczak, D., Lepesant, J. A. and Antoniewski, C., (2003). Absence of transitive and systemic pathways allows cell-specific and isoform-specific RNAi in Drosophila. RNA, 9, 299–308CrossRef Google Scholar PubMed

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, 487–491CrossRef Google Scholar PubMed

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, 537–548CrossRef Google Scholar

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, 199–208CrossRef Google Scholar PubMed

Sen, G. C., Lebleu, B., Brown, G. E., Kawakita, M., Slattery, E., and Lengyel, P., (1976). Interferon, double-stranded RNA and mRNA degradation. Nature, 264, 370–373CrossRef Google Scholar PubMed

Sharp, P. A. (1999). RNAi and double-strand RNA. Genes & Development, 13, 139–141CrossRef Google Scholar PubMed

Sharp, P. A. (2001). RNA interference – 2001. Genes & Development, 15, 485–490CrossRef Google Scholar PubMed

Shramke, V. and Allshire, R., (2003) Hairpin RNAs and retrotransposon LTRs effect RNAi and chromatin-based gene silencing. Science, 301, 1069–1074CrossRef Google Scholar

Sijen, T., Fleenor, J., Simmer, F., Thijssen, K. L., Parrish, S., Timmons, L., Plasterk, R. H. and Fire, A. (2001). On the role of RNA amplification in dsRNA-triggered gene silencing. Cell, 107, 465–476CrossRef Google Scholar PubMed

Simmer, F., Tijsterman, M., Parrish, S., Koushika, S. P., Nonet, M. L., Fire, A., Ahringer, J., and Plasterk, R. H. (2002). Loss of the putative RNA-directed RNA polymerase RRF-3 makes C. elegans hypersensitive to RNAi. Current Biology, 12, 1317–1319CrossRef Google Scholar PubMed

Smardon, A., Spoerke, J. M., Stacey, S. C., Klein, M. E., Mackin, N., and Maine, E. M. (2000). EGO-1 is related to RNA-directed RNA polymerase and functions in germ-line development and RNA interference in C. elegans. Current Biology, 10, 169–178CrossRef Google Scholar PubMed

Stark, G. R., Kerr, I. M., Williams, B. R., Silverman, R. H. and Schreiber, R. D. (1998). How cells respond to interferons. Annual Reviews of Biochemistry, 67, 227–264CrossRef Google Scholar PubMed

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, 123–132CrossRef Google Scholar PubMed

Tabara, H., Yigit, E., Siomi, H., and Mello, C. C. (2002). The dsRNA binding protein RDE-4 interacts with RDE-1, DCR-1, and a DExH-box helicase to direct RNAi in C. elegans. Cell, 109, 861–871CrossRef Google Scholar

Tijsterman, M., Ketting, R. F. and Plasterk, R. H. (2002a). The genetics of RNA silencing. Annual Reviews of Genetics, 36, 489–519CrossRef Google Scholar

Tijsterman, M., Ketting, R. F., Okihara, K. L., Sijen, T., and Plasterk, R. H. (2002b). RNA helicase MUT-14-dependent gene silencing triggered in C. elegans by short antisense RNAs. Science, 295, 694–697CrossRef Google Scholar

Vaucheret, H., Beclin, C., and Fagard, M., (2001). post-transcriptional gene silencing in plants. Journal of Cell Sience, 114, 3083–3091Google Scholar PubMed

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, 1833–1837CrossRef Google Scholar PubMed

Wargelius, A., Ellingsen, S., and Fjose, A., (1999). Double-stranded RNA induces specific developmental defects in zebrafish embryos. Biochemical Biophysical Research Communications, 263, 156–1561CrossRef Google Scholar PubMed

Wianny, F. and Zernicka-Goetz, M. (2000). Specific interference with gene function by double-stranded RNA in early mouse development. Nature Cell Biology, 2, 70–75CrossRef Google Scholar PubMed

Williams, R. W. and Rubin, G. M. (2002). ARGONAUTE1 is required for efficient RNA interference in Drosophila embryos. Proceedings of the National Academy of Sciences USA, 99, 6889–6894CrossRef Google Scholar PubMed

Winston, W. M., Molodowitch, C., and Hunter, C. P. (2002). Systemic RNAi in C. elegans requires the putative transmembrane protein SID-1. Science, 295, 2456–2459CrossRef Google Scholar

Wu-Scharf, D., Jeong, B., Zhang, C., and Cerutti, H., (2000). Transgene and transposon silencing in Chlamydomonas reinhardtii by a DEAH-box RNA helicase. Science, 290, 1159–1162CrossRef Google Scholar PubMed

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, 25–33CrossRef Google Scholar PubMed

Zamore, P. D. (2002). Ancient pathways programmed by small RNAs. Science, 296, 1265–1269CrossRef Google Scholar PubMed

Zilberman, D, Cao, X. and Jacobsen, S. E. (2003). ARGONAUTE4 control of locus-specific siRNA accumulation and DNA and histone methylation. Science, 299, 716–719CrossRef Google Scholar PubMed

Accessibility standard: Unknown

Why this information is here

This section outlines the accessibility features of this content - including support for screen readers, full keyboard navigation and high-contrast display options. This may not be relevant for you.

Accessibility Information

Accessibility compliance for the PDF of this chapter is currently unknown and may be updated in the future.