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RNA interference in Caenorhabditis elegans: Uptake, mechanism, and regulation

Published online by Cambridge University Press:  11 November 2011

JIMMY J. ZHUANG  and
CRAIG P. HUNTER
JIMMY J. ZHUANG
Affiliation:
Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA
CRAIG P. HUNTER*
Affiliation:
Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA
*
*Corresponding author: Tel: (617) 495-8309. Fax: (617) 496-0132. Email: [email protected]
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Summary

RNA interference (RNAi) is a powerful research tool that has enabled molecular insights into gene activity, pathway analysis, partial loss-of-function phenotypes, and large-scale genomic discovery of gene function. While RNAi works extremely well in the non-parasitic nematode C. elegans, it is also especially useful in organisms that lack facile genetic analysis. Extensive genetic analysis of the mechanisms, delivery and regulation of RNAi in C. elegans has provided mechanistic and phenomenological insights into why RNAi is so effective in this species. These insights are useful for the testing and development of RNAi in other nematodes, including parasitic nematodes where more effective RNAi would be extremely useful. Here, we review the current advances in C. elegans for RNA delivery methods, regulation of cell autonomous and systemic RNAi phenomena, and implications of enhanced RNAi mutants. These discussions, with a focus on mechanism and cross-species application, provide new perspectives for optimizing RNAi in other species.

Keywords

Caenorhabditis elegans RNA interferencereverse genetics methodsRNAi transportRNAi regulationsystemic RNAiautonomous RNAi
Type
Research Article
Information
Parasitology , Volume 139 , Special Issue 5: Genetic manipulation of parasitic helminths to define gene function , April 2012 , pp. 560 - 573
Copyright
Copyright © Cambridge University Press 2011

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References

REFERENCES

Alder, M. N., Dames, S., Gaudet, J. and Mango, S. E. (2003). Gene silencing in Caenorhabditis elegans by transitive RNA interference. RNA 9, 25–32.Google Scholar
Altschul, S. F., Madden, T. L., Schaffer, A. A., Zhang, J., Zhang, Z., Miller, W. and Lipman, D. J. (1997). Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Research 25, 3389–3402. doi: gka562 (Allo and Kornblihtt).CrossRefGoogle ScholarPubMed
Ansel, K. M., Pastor, W. A., Rath, N., Lapan, A. D., Glasmacher, E., Wolf, C., Smith, L. C., Papadopoulou, N., Lamperti, E. D., Tahiliani, M., Ellwart, J. W., Shi, Y., Kremmer, E., Rao, A. and Heissmeyer, V. (2008). Mouse Eri1 interacts with the ribosome and catalyzes 5 8S rRNA processing. Nature Structural and Molecular Biology 15, 523–530. doi: nsmb.1417 (Allo and Kornblihtt) 10.1038/nsmb.1417.CrossRefGoogle ScholarPubMed
Asikainen, S., Storvik, M., Lakso, M. and Wong, G. (2007). Whole genome microarray analysis of C. elegans rrf-3 and eri-1 mutants. FEBS Letters 581, 5050–5054. doi: S0014-5793(07)01025-3 [pii] 10.1016/j.febslet.2007.09.043.Google Scholar
Bartscherer, K., Pelte, N., Ingelfinger, D. and Boutros, M. (2006). Secretion of Wnt ligands requires Evi, a conserved transmembrane protein. Cell 125, 523–533. doi: S0092-8674(06)00451-X [pii] 10.1016/j.cell.2006.04.009.CrossRefGoogle ScholarPubMed
Boudreau, R. L., Monteys, A. M. and Davidson, B. L. (2008). Minimizing variables among hairpin-based RNAi vectors reveals the potency of shRNAs. RNA 14, 1834–1844. doi: rna.1062908 [pii] 10.1261/rna.1062908.Google Scholar
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, 263–264. doi: 10.1038/ng1173 ng1173 [pii].CrossRefGoogle ScholarPubMed
Calixto, A., Chelur, D., Topalidou, I., Chen, X. and Chalfie, M. (2010). Enhanced neuronal RNAi in C. elegans using SID-1. Nature Methods 7, 554–559. doi: nmeth.1463 [pii] 10.1038/nmeth.1463.CrossRefGoogle Scholar
Carpenter, A. E. and Sabatini, D. M. (2004). Systematic genome-wide screens of gene function. Nature Reviews Genetics 5, 11–22. doi: 10.1038/nrg1248nrg1248 [pii].CrossRefGoogle ScholarPubMed
Chekulaeva, M. and Filipowicz, W. (2009). Mechanisms of miRNA-mediated post-transcriptional regulation in animal cells. Current Opinion in Cell Biology 21, 452–460. doi: 10.1016/j.ceb.2009.04.009.CrossRefGoogle ScholarPubMed
Claycomb, J. M., Batista, P. J., Pang, K. M., Gu, W., Vasale, J. J., van Wolfswinkel, J. C., Chaves, D. A., Shirayama, M., Mitani, S., Ketting, R. F., Conte, D. Jr. and Mello, C. C. (2009). The Argonaute CSR-1 and its 22G-RNA cofactors are required for holocentric chromosome segregation. Cell 139, 123–134. doi: S0092-8674(09)01174-X [pii] 10.1016/j.cell.2009.09.014.Google Scholar
Conine, C. C., Batista, P. J., Gu, W., Claycomb, J. M., Chaves, D. A., Shirayama, M. and Mello, C. C. (2010). Argonautes ALG-3 and ALG-4 are required for spermatogenesis-specific 26G-RNAs and thermotolerant sperm in Caenorhabditis elegans. Proceedings of the National Academy of Sciences, USA 107, 3588–3593. doi: 0911685107 [pii] 10.1073/pnas.0911685107.CrossRefGoogle ScholarPubMed
Crombach, A. and Hogeweg, P. (2011). Is RNA-dependent RNA polymerase essential for transposon control? BMC Systems Biology 5, 104. doi: 10.1186/1752-0509-5-104.CrossRefGoogle Scholar
Cullen, B. R. (2006). Is RNA interference involved in intrinsic antiviral immunity in mammals? Nature Immunology 7, 563–567. doi: ni1352 [pii] 10.1038/ni1352.Google Scholar
Czech, B. and Hannon, G. J. (2011). Small RNA sorting: matchmaking for Argonautes. Nature Reviews Genetics 12, 19–31. doi: nrg2916 [pii] 10.1038/nrg2916.CrossRefGoogle ScholarPubMed
Dalzell, J. J., McVeigh, P., Warnock, N. D., Mitreva, M., Bird, D. M., Abad, P., Fleming, C. C., Day, T. A., Mousley, A., Marks, N. J. and Maule, A. G. (2011). RNAi Effector Diversity in Nematodes. PLoS Neglected Tropical Diseases 5, e1176. doi: 10.1371/journal.pntd.0001176PNTD-D-11-00183 [pii].CrossRefGoogle ScholarPubMed
Ding, S. W. (2010). RNA-based antiviral immunity. Nature Reviews Immunology 10, 632–644. doi: nri2824 [pii] 10.1038/nri2824.CrossRefGoogle ScholarPubMed
Ding, L., Spencer, A., Morita, K. and Han, M. (2005). The developmental timing regulator AIN-1 interacts with miRISCs and may target the argonaute protein ALG-1 to cytoplasmic P bodies in C. elegans. Molecular Cell 19, 437–447. doi: S1097-2765(05)01477-2 [pii] 10.1016/j.molcel.2005.07.013.CrossRefGoogle ScholarPubMed
Duchaine, T. F., Wohlschlegel, J. A., Kennedy, S., Bei, Y., Conte, D. Jr., Pang, K., Brownell, D. R., Harding, S., Mitani, S., Ruvkun, G., Yates, J. R. 3rd and Mello, C. C. (2006). Functional proteomics reveals the biochemical niche of C. elegans DCR-1 in multiple small-RNA-mediated pathways. Cell 124, 343–354. doi: S0092-8674(05)01394-2 [pii] 10.1016/j.cell.2005.11.036.CrossRefGoogle ScholarPubMed
Echeverri, C. J., Beachy, P. A., Baum, B., Boutros, M., Buchholz, F., Chanda, S. K., Downward, J., Ellenberg, J., Fraser, A. G., Hacohen, N., Hahn, W. C., Jackson, A. L., Kiger, A., Linsley, P. S., Lum, L., Ma, Y., Mathey-Prevot, B., Root, D. E., Sabatini, D. M., Taipale, J., Perrimon, N. and Bernards, R. (2006). Minimizing the risk of reporting false positives in large-scale RNAi screens. Nature Methods 3, 777–779. doi: nmeth1006-777 [pii] 10.1038/nmeth1006-777.Google Scholar
Fagard, M. and Vaucheret, H. (2000). Systemic silencing signal(s). Plant Molecular Biology 43, 285–293.CrossRefGoogle ScholarPubMed
Feinberg, E. H. and Hunter, C. P. (2003). Transport of dsRNA into cells by the transmembrane protein SID-1. Science 301, 1545–1547. doi: 10.1126/science.1087117301/5639/1545 [pii].CrossRefGoogle ScholarPubMed
Felix, M. A. (2008). RNA interference in nematodes and the chance that favored Sydney Brenner. Journal of Biology 7, 34. doi: jbiol97 [pii] 10.1186/jbiol97.Google Scholar
Felix, M. A., Ashe, A., Piffaretti, J., Wu, G., Nuez, I., Belicard, T., Jiang, Y., Zhao, G., Franz, C. J., Goldstein, L. D., Sanroman, M., Miska, E. A. and Wang, D. (2011). Natural and experimental infection of Caenorhabditis nematodes by novel viruses related to nodaviruses. PLoS Biology 9, e1000586. doi: 10.1371/journal.pbio.1000586.Google Scholar
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, 806–811. doi: 10.1038/35888.Google Scholar
Fischer, S. E., Butler, M. D., Pan, Q. and Ruvkun, G. (2008). Trans-splicing in C. elegans generates the negative RNAi regulator ERI-6/7. Nature 455, 491–496. doi: nature07274 [pii] 10.1038/nature07274.Google Scholar
Fraser, A. G., Kamath, R. S., Zipperlen, P., Martinez-Campos, M., Sohrmann, M. and Ahringer, J. (2000). Functional genomic analysis of C. elegans chromosome I by systematic RNA interference. Nature 408, 325–330. doi: 10.1038/35042517.CrossRefGoogle ScholarPubMed
Geldhof, P., Murray, L., Couthier, A., Gilleard, J. S., McLauchlan, G., Knox, D. P. and Britton, C. (2006). Testing the efficacy of RNA interference in Haemonchus contortus. International Journal for Parasitology 36, 801–810. doi: S0020-7519(05)00422-4 [pii] 10.1016/j.ijpara.2005.12.004.Google Scholar
Geldhof, P., Visser, A., Clark, D., Saunders, G., Britton, C., Gilleard, J., Berriman, M. and Knox, D. (2007). RNA interference in parasitic helminths: current situation, potential pitfalls and future prospects. Parasitology 134, 609–619. doi: S0031182006002071 [pii] 10.1017/S0031182006002071.CrossRefGoogle ScholarPubMed
Gent, J. I., Lamm, A. T., Pavelec, D. M., Maniar, J. M., Parameswaran, P., Tao, L., Kennedy, S. and Fire, A. Z. (2010). Distinct phases of siRNA synthesis in an endogenous RNAi pathway in C. elegans soma. Molecular Cell 37, 679–689. doi: S1097-2765(10)00041-9 [pii] 10.1016/j.molcel.2010.01.012.Google Scholar
Gent, J. I., Schvarzstein, M., Villeneuve, A. M., Gu, S. G., Jantsch, V., Fire, A. Z. and Baudrimont, A. (2009). A Caenorhabditis elegans RNA-directed RNA polymerase in sperm development and endogenous RNA interference. Genetics 183, 1297–1314. doi: genetics.109.109686 [pii] 10.1534/genetics.109.109686.Google Scholar
Gille, C. (2006). Structural interpretation of mutations and SNPs using STRAP-NT. Protein Science 15, 208–210. doi:10.1110/ps.051882006[pii].CrossRefGoogle ScholarPubMed
Grimson, A., Srivastava, M., Fahey, B., Woodcroft, B. J., Chiang, H. R., King, N., Degnan, B. M., Rokhsar, D. S. and Bartel, D. P. (2008). Early origins and evolution of microRNAs and Piwi-interacting RNAs in animals. Nature 455, 1193–1197. doi: nature07415 [pii] 10.1038/nature07415.Google Scholar
Grishok, A. and Mello, C. C. (2002). RNAi (Nematodes: Caenorhabditis elegans). Advances in Genetics 46, 339–360.Google Scholar
Grishok, A., Sinskey, J. L. and Sharp, P. A. (2005). Transcriptional silencing of a transgene by RNAi in the soma of C. elegans. Genes and Development 19, 683–696. doi: gad.1247705 [pii] 10.1101/gad.1247705.CrossRefGoogle ScholarPubMed
Grove, C. A., De Masi, F., Barrasa, M. I., Newburger, D. E., Alkema, M. J., Bulyk, M. L. and Walhout, A. J. (2009). A multiparameter network reveals extensive divergence between C. elegans bHLH transcription factors. Cell 138, 314–327. doi: S0092-8674(09)00519-4 [pii] 10.1016/j.cell.2009.04.058.CrossRefGoogle ScholarPubMed
Guang, S., Bochner, A. F., Burkhart, K. B., Burton, N., Pavelec, D. M. and Kennedy, S. (2010). Small regulatory RNAs inhibit RNA polymerase II during the elongation phase of transcription. Nature 465, 1097–1101. doi: nature09095 [pii] 10.1038/nature09095.Google Scholar
Guang, S., Bochner, A. F., Pavelec, D. M., Burkhart, K. B., Harding, S., Lachowiec, J. and Kennedy, S. (2008). An Argonaute transports siRNAs from the cytoplasm to the nucleus. Science, 321(5888), 537–541. doi: 321/5888/537 [pii] 10.1126/science.1157647.Google Scholar
Habig, J. W., Aruscavage, P. J. and Bass, B. L. (2008). In C. elegans, high levels of dsRNA allow RNAi in the absence of RDE-4. PLoS One 3, e4052. doi: 10.1371/journal.pone.0004052.Google Scholar
Hall, T. M. (2005). Structure and function of argonaute proteins. Structure 13, 1403–1408. doi: S0969-2126(05)00305-9 [pii] 10.1016/j.str.2005.08.005.Google Scholar
Hannon, G. J. (2002). RNA interference. Nature 418, 244–251. doi: 10.1038/418244a418244a [pii].CrossRefGoogle ScholarPubMed
Huntzinger, E. and Izaurralde, E. (2011). Gene silencing by microRNAs: contributions of translational repression and mRNA decay. Nature Reviews Genetics 12, 99–110. doi: nrg2936 [pii] 10.1038/nrg2936.Google Scholar
Issa, Z., Grant, W. N., Stasiuk, S. and Shoemaker, C. B. (2005). Development of methods for RNA interference in the sheep gastrointestinal parasite, Trichostrongylus colubriformis. International Journal for Parasitology 35, 935–940. doi: S0020-7519(05)00183-9 [pii] 10.1016/j.ijpara.2005.06.001.Google Scholar
Jakymiw, A., Lian, S., Eystathioy, T., Li, S., Satoh, M., Hamel, J. C., Fritzler, M. J. and Chan, E. K. (2005). Disruption of GW bodies impairs mammalian RNA interference. Nature Cell Biology 7, 1267–1274. doi: ncb1334 [pii] 10.1038/ncb1334.CrossRefGoogle ScholarPubMed
Jose, A. M. and Hunter, C. P. (2007). Transport of sequence-specific RNA interference information between cells. Annual Review of Genetics 41, 305–330. doi: 10.1146/annurev.genet.41.110306.130216.Google Scholar
Jose, A. M., Smith, J. J. and Hunter, C. P. (2009). Export of RNA silencing from C. elegans tissues does not require the RNA channel SID-1. Proceedings of the National Academy of Sciences, USA 106, 2283–2288. doi: 0809760106 [pii] 10.1073/pnas.0809760106.CrossRefGoogle Scholar
Kamath, R. S. and Ahringer, J. (2003). Genome-wide RNAi screening in Caenorhabditis elegans. Methods 30, 313–321. doi: S1046202303000501 [pii].Google Scholar
Kamath, R. S., Fraser, A. G., Dong, Y., Poulin, G., Durbin, R., Gotta, M., Kanapin, A., Le 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, 231–237. doi: 10.1038/nature01278nature01278 [pii].Google Scholar
Kelley, L. A. and Sternberg, M. J. (2009). Protein structure prediction on the Web: a case study using the Phyre server. Nature Protocols 4, 363–371. doi: nprot.2009.2 [pii] 10.1038/nprot.2009.2.Google Scholar
Kennedy, S., Wang, D. and Ruvkun, G. (2004). A conserved siRNA-degrading RNase negatively regulates RNA interference in C. elegans. Nature 427, 645–649. doi: 10.1038/nature02302nature02302 [pii].Google Scholar
Kim, D. H., Behlke, M. A., Rose, S. D., Chang, M. S., Choi, S. and Rossi, J. J. (2005 a). Synthetic dsRNA Dicer substrates enhance RNAi potency and efficacy. Nature Biotechnology 23, 222–226. doi: nbt1051 [pii] 10.1038/nbt1051.Google Scholar
Kim, J. K., Gabel, H. W., Kamath, R. S., Tewari, M., Pasquinelli, A., Rual, J. F., Kennedy, S., Dybbs, M., Bertin, N., Kaplan, J. M., Vidal, M. and Ruvkun, G. (2005 b). Functional genomic analysis of RNA interference in C. elegans. Science 308, 1164–1167. doi: 1109267 [pii] 10.1126/science.1109267.Google Scholar
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, 2269–2271. doi: 10.1126/science.10620391062039 [pii].CrossRefGoogle ScholarPubMed
Knox, D. P., Geldhof, P., Visser, A. and Britton, C. (2007). RNA interference in parasitic nematodes of animals: a reality check? Trends in Parasitology 23, 105–107. doi: S1471-4922(07)00021-9 [pii] 10.1016/j.pt.2007.01.007.CrossRefGoogle ScholarPubMed
Krautz-Peterson, G., Radwanska, M., Ndegwa, D., Shoemaker, C. B. and Skelly, P. J. (2007). Optimizing gene suppression in schistosomes using RNA interference. Molecular and Biochemical Parasitology 153, 194–202. doi: S0166-6851(07)00076-X [pii] 10.1016/j.molbiopara.2007.03.006.Google Scholar
Krueger, U., Bergauer, T., Kaufmann, B., Wolter, I., Pilk, S., Heider-Fabian, M., Kirch, S., Artz-Oppitz, C., Isselhorst, M. and Konrad, J. (2007). Insights into effective RNAi gained from large-scale siRNA validation screening. Oligonucleotides 17, 237–250. doi: 10.1089/oli.2006.0065.Google Scholar
Kuwabara, P. E. and Coulson, A. (2000). RNAi–prospects for a general technique for determining gene function. Parasitology Today 16, 347–349. doi: S0169-4758(00)01677-X [pii].Google Scholar
Lee, R. C., Hammell, C. M. and Ambros, V. (2006). Interacting endogenous and exogenous RNAi pathways in Caenorhabditis elegans. RNA 12, 589–597. doi: rna.2231506 [pii] 10.1261/rna.2231506.Google Scholar
Liu, J., Valencia-Sanchez, M. A., Hannon, G. J. and Parker, R. (2005). MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nature Cell Biology 7, 719–723. doi: ncb1274 [pii] 10.1038/ncb1274.Google Scholar
Lu, R., Maduro, M., Li, F., Li, H. W., Broitman-Maduro, G., Li, W. X. and Ding, S. W. (2005). Animal virus replication and RNAi-mediated antiviral silencing in Caenorhabditis elegans. Nature 436, 1040–1043. doi: nature03870 [pii] 10.1038/nature03870.Google Scholar
Macrae, I. J., Zhou, K., Li, F., Repic, A., Brooks, A. N., Cande, W. Z., Adams, P. D. and Doudna, J. A. (2006). Structural basis for double-stranded RNA processing by Dicer. Science 311, 195–198. doi: 311/5758/195 [pii] 10.1126/science.1121638.Google Scholar
Maeda, I., Kohara, Y., Yamamoto, M. and Sugimoto, A. (2001). Large-scale analysis of gene function in Caenorhabditis elegans by high-throughput RNAi. Current Biology 11, 171–176. doi: S0960-9822(01)00052-5 [pii].CrossRefGoogle ScholarPubMed
Maida, Y. and Masutomi, K. (2011). RNA-dependent RNA polymerases in RNA silencing. Biological Chemistry 392, 299–304. doi: 10.1515/BC.2011.035.Google Scholar
Mikuma, T., Kawasaki, H., Yamamoto, Y. and Taira, K. (2004). Overexpression of Dicer enhances RNAi-mediated gene silencing by short-hairpin RNAs (shRNAs) in human cells. Nucleic Acids Symposium Series (Oxford Journals) 48, 191–192. doi: 48/1/191 [pii] 10.1093/nass/48.1.191.Google Scholar
Mittal, V. (2004). Improving the efficiency of RNA interference in mammals. Nature Reviews Genetics 5, 355–365. doi: 10.1038/nrg1323nrg1323 [pii].Google Scholar
Moazed, D. (2009). Small RNAs in transcriptional gene silencing and genome defence. Nature 457, 413–420. doi: 10.1038/Nature07756.Google Scholar
Mochizuki, K. (2010). RNA-directed epigenetic regulation of DNA rearrangements. Essays in Biochemistry 48, 89–100. doi: bse0480089 [pii] 10.1042/bse0480089.Google ScholarPubMed
Motamedi, M. R., Verdel, A., Colmenares, S. U., Gerber, S. A., Gygi, S. P. and Moazed, D. (2004). Two RNAi complexes, RITS and RDRC, physically interact and localize to noncoding centromeric RNAs. Cell 119, 789–802. doi: S009286740401102X [pii] 10.1016/j.cell.2004.11.034.Google Scholar
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, 533–542. doi: S0092-8674(00)80863-6 [pii].CrossRefGoogle ScholarPubMed
Nasevicius, A. and Ekker, S. C. (2000). Effective targeted gene ‘knockdown’ in zebrafish. Nature Genetics 26, 216–220. doi: 10.1038/79951.CrossRefGoogle ScholarPubMed
Paddison, P. J. and Vogt, P. K. (Eds.) (2008). RNA Interference, Springer, Heidelberg, Germany.Google Scholar
Pak, J. and Fire, A. (2007). Distinct populations of primary and secondary effectors during RNAi in C. elegans. Science 315, 241–244. doi: 1132839 [pii] 10.1126/science.1132839.Google Scholar
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, 315–327. doi: S1097276502004409 [pii].Google Scholar
Parrish, S. and Fire, A. (2001). Distinct roles for RDE-1 and RDE-4 during RNA interference in Caenorhabditis elegans. RNA 7, 1397–1402.Google Scholar
Pavelec, D. M., Lachowiec, J., Duchaine, T. F., Smith, H. E. and Kennedy, S. (2009). Requirement for the ERI/DICER complex in endogenous RNA interference and sperm development in Caenorhabditis elegans. Genetics 183, 1283–1295. doi: genetics.109.108134 [pii] 10.1534/genetics.109.108134.Google Scholar
Perrimon, N., Ni, J. Q. and Perkins, L. (2010). In vivo RNAi: today and tomorrow. Cold Spring Harbor Perspectives in Biology 2, 1–11. a003640. doi: cshperspect.a003640 [pii] 10.1101/cshperspect.a003640.Google Scholar
Praitis, V., Casey, E., Collar, D. and Austin, J. (2001). Creation of low-copy integrated transgenic lines in Caenorhabditis elegans. Genetics 157, 1217–1226.Google Scholar
Rea, S. L., Ventura, N. and Johnson, T. E. (2007). Relationship between mitochondrial electron transport chain dysfunction, development, and life extension in Caenorhabditis elegans. PLoS Biology 5, 2312–2329.Google Scholar
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, 299–308.Google Scholar
Rual, J. F., Ceron, J., Koreth, J., Hao, T., Nicot, A. S., Hirozane-Kishikawa, T., Vandenhaute, J., Orkin, S. H., Hill, D. E., van den Heuvel, S. and Vidal, M. (2004). Toward improving Caenorhabditis elegans phenome mapping with an ORFeome-based RNAi library. Genome Research 14, 2162–2168. doi: 14/10b/2162 [pii] 10.1101/gr.2505604.Google Scholar
Saleh, M. C., Tassetto, M., van Rij, R. P., Goic, B., Gausson, V., Berry, B., Jacquier, C., Antoniewski, C. and Andino, R. (2009). Antiviral immunity in Drosophila requires systemic RNA interference spread. Nature 458, 346–350. doi: nature07712 [pii] 10.1038/nature07712.Google Scholar
Saleh, M. C., van Rij, R. P., Hekele, A., Gillis, A., Foley, E., O'Farrell, P. H. and Andino, R. (2006). The endocytic pathway mediates cell entry of dsRNA to induce RNAi silencing. Nature Cell Biology 8, 793–802. doi: ncb1439 [pii] 10.1038/ncb1439.Google Scholar
Schepers, U. (2005). RNA Interference in Practice, Wiley-VCH, Weinheim.Google Scholar
Schott, D. H., Cureton, D. K., Whelan, S. P. and Hunter, C. P. (2005). An antiviral role for the RNA interference machinery in Caenorhabditis elegans. Proceedings of the National Academy of Sciences, USA 102, 18420–18424. doi: 0507123102 [pii] 10.1073/pnas.0507123102.Google Scholar
Shabalina, S. A. and Koonin, E. V. (2008). Origins and evolution of eukaryotic RNA interference. Trends in Ecology and Evolution 23, 578–587. doi: S0169-5347(08)00243-7 [pii] 10.1016/j.tree.2008.06.005.CrossRefGoogle ScholarPubMed
Sharp, P. A. (1999). RNAi and double-strand RNA. Genes and Development 13, 139–141.Google Scholar
Shih, J. D., Fitzgerald, M. C., Sutherlin, M. and Hunter, C. P. (2009). The SID-1 double-stranded RNA transporter is not selective for dsRNA length. RNA 15, 384–390. doi: rna.1286409 [pii] 10.1261/rna.1286409.Google Scholar
Shih, J. D. and Hunter, C. P. (2011). SID-1 is a dsRNA-selective dsRNA-gated channel. RNA 17, 1057–1065. doi: rna.2596511 [pii] 10.1261/rna.2596511.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, 465–476. doi: S0092-8674(01)00576-1 [pii].Google Scholar
Sijen, T. and Plasterk, R. H. (2003). Transposon silencing in the Caenorhabditis elegans germ line by natural RNAi. Nature 426, 310–314. doi: 10.1038/nature02107nature02107 [pii].Google Scholar
Silva, J., Chang, K., Hannon, G. J. and Rivas, F. V. (2004). RNA-interference-based functional genomics in mammalian cells: reverse genetics coming of age. Oncogene 23, 8401–8409. doi: 1208176 [pii] 10.1038/sj.onc.1208176.Google Scholar
Simmer, F., Moorman, C., van der Linden, A. M., Kuijk, E., van den Berghe, P. V., Kamath, R. S., Fraser, A. G., Ahringer, J. and Plasterk, R. H. (2003). Genome-wide RNAi of C. elegans using the hypersensitive rrf-3 strain reveals novel gene functions. PLoS Biology 1, E12. doi: 10.1371/journal.pbio.0000012.Google Scholar
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, 1317–1319. doi: S0960982202010412 [pii].Google Scholar
Sioud, M. (2011). Promises and challenges in developing RNAi as a research tool and therapy. Methods in Molecular Biology 703, 173–187. doi: 10.1007/978-1-59745-248-9_12.CrossRefGoogle ScholarPubMed
Sledz, C. A., Holko, M., de Veer, M. J., Silverman, R. H. and Williams, B. R. (2003). Activation of the interferon system by short-interfering RNAs. Nature Cell Biology 5, 834–839. doi: 10.1038/ncb1038ncb1038 [pii].Google Scholar
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, 169–178. doi: S0960-9822(00)00323-7 [pii].Google Scholar
Song, J. J., Smith, S. K., Hannon, G. J. and Joshua-Tor, L. (2004). Crystal structure of Argonaute and its implications for RISC slicer activity. Science 305, 1434–1437. doi: 10.1126/science.11025141102514 [pii].Google Scholar
Steiner, F. A., Okihara, K. L., Hoogstrate, S. W., Sijen, T. and Ketting, R. F. (2009). RDE-1 slicer activity is required only for passenger-strand cleavage during RNAi in Caenorhabditis elegans. Nature Structural and Molecular Biology 16, 207–211. doi: nsmb.1541 [pii] 10.1038/nsmb.1541.Google Scholar
Svoboda, P. and Stein, P. (2009). RNAi experiments in mouse oocytes and early embryos. Cold Spring Harbor Protocols, 2009(1), pdb top56. doi: 2009/1/pdb.top56 [pii] 10.1101/pdb.top56.Google Scholar
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, 123–132. doi: S0092-8674(00)81644-X [pii].Google Scholar
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, 861–871. doi: S0092867402007936 [pii].Google Scholar
Teixeira, F. K. and Colot, V. (2010). Repeat elements and the Arabidopsis DNA methylation landscape. Heredity 105, 14–23. doi: hdy201052 [pii] 10.1038/hdy.2010.52.Google Scholar
Tijsterman, M., Okihara, K. L., Thijssen, K. and Plasterk, R. H. A. (2002). PPW-1, a PAZ/PIWI protein required for efficient germline RNAi, is defective in a natural isolate of C. elegans. Current Biology 12, 1535–1540. doi:10.1016/S0960-9822(02)01110-7.Google Scholar
Timmons, L., Court, D. L. and Fire, A. (2001). Ingestion of bacterially expressed dsRNAs can produce specific and potent genetic interference in Caenorhabditis elegans. Gene 263, 103–112. doi: S0378111900005795 [pii].Google Scholar
Timmons, L. and Fire, A. (1998). Specific interference by ingested dsRNA. Nature 395, 854. doi: 10.1038/27579.CrossRefGoogle ScholarPubMed
Tomari, Y., Matranga, C., Haley, B., Martinez, N. and Zamore, P. D. (2004). A protein sensor for siRNA asymmetry. Science 306, 1377–1380. doi: 306/5700/1377 [pii] 10.1126/science.1102755.CrossRefGoogle ScholarPubMed
Tomoyasu, Y., Miller, S. C., Tomita, S., Schoppmeier, M., Grossmann, D. and Bucher, G. (2008). Exploring systemic RNA interference in insects: a genome-wide survey for RNAi genes in Tribolium. Genome Biology 9, R10. doi: gb-2008-9-1-r10 [pii] 10.1186/gb-2008-9-1-r10.Google Scholar
Ulvila, J., Parikka, M., Kleino, A., Sormunen, R., Ezekowitz, R. A., Kocks, C. and Rämet, M. (2006). Double-stranded RNA is internalized by scavenger-mediated endocytosis in Drosophila S2 cells. Journal of Biological Chemistry 281, 14370–14375. doi: 10.1074/jbc.M513868200 [pii].CrossRefGoogle Scholar
Vance, V. and Vaucheret, H. (2001). RNA silencing in plants –defense and counterdefense. Science 292, 2277–2280. doi: 10.1126/science.1061334292/5525/2277 [pii].Google Scholar
Vasale, J. J., Gu, W., Thivierge, C., Batista, P. J., Claycomb, J. M., Youngman, E. M., Duchaine, T. F., Mello, C. C. and Conte, D. Jr. (2010). Sequential rounds of RNA-dependent RNA transcription drive endogenous small-RNA biogenesis in the ERGO-1/Argonaute pathway. Proceedings of the National Academy of Sciences, USA 107, 3582–3587. doi: 0911908107 [pii] 10.1073/pnas.0911908107.Google Scholar
Visser, A., Geldhof, P., de Maere, V., Knox, D. P., Vercruysse, J. and Claerebout, E. (2006). Efficacy and specificity of RNA interference in larval life-stages of Ostertagia ostertagi. Parasitology 133, 777–783. doi: S0031182006001004 [pii] 10.1017/S0031182006001004.Google Scholar
Wang, D., Kennedy, S., Conte, D. Jr., Kim, J. K., Gabel, H. W., Kamath, R. S., Mello, C. C. and Ruvkun, G. (2005). Somatic misexpression of germline P granules and enhanced RNA interference in retinoblastoma pathway mutants. Nature 436, 593–597. doi: nature04010 [pii] 10.1038/nature04010.Google Scholar
Welker, N. C., Pavelec, D. M., Nix, D. A., Duchaine, T. F., Kennedy, S. and Bass, B. L. (2010). Dicer's helicase domain is required for accumulation of some, but not all, C. elegans endogenous siRNAs. RNA 16, 893–903. doi: rna.2122010 [pii] 10.1261/rna.2122010.Google Scholar
Whangbo, J. S. and Hunter, C. P. (2008). Environmental RNA interference. Trends in Genetics 24, 297–305. doi:10.1016./j.tig.2008.03.007[pii].Google Scholar
White, S. A. and Allshire, R. C. (2008). RNAi-mediated chromatin silencing in fission yeast. Current Topics in Microbiology and Immunology 320, 157–183.Google Scholar
Wilkins, C., Dishongh, R., Moore, S. C., Whitt, M. A., Chow, M. and Machaca, K. (2005). RNA interference is an antiviral defence mechanism in Caenorhabditis elegans. Nature 436, 1044–1047. doi: nature03957 [pii] 10.1038/nature03957.CrossRefGoogle 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, 2456–2459. doi: 10.1126/science.10688361068836 [pii].Google Scholar
Winston, W. M., Sutherlin, M., Wright, A. J., Feinberg, E. H. and Hunter, C. P. (2007). Caenorhabditis elegans SID-2 is required for environmental RNA interference. Proceedings of the National Academy of Sciences, USA, 104, 10565–10570. doi: 0611282104 [pii] 10.1073/pnas.0611282104.Google Scholar
Yadav, B. C., Veluthambi, K. and Subramaniam, K. (2006). Host-generated double stranded RNA induces RNAi in plant-parasitic nematodes and protects the host from infection. Molecular and Biochemical Parasitology 148, 219–222. doi: S0166-6851(06)00111-3 [pii] 10.1016/j.molbiopara.2006.03.013.Google Scholar
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, 1191–1200. doi: S0960-9822(00)00732-6 [pii].CrossRefGoogle ScholarPubMed
Yigit, E., Batista, P. J., Bei, Y., Pang, K. M., Chen, C. C., Tolia, N. H., Joshua-Tor, L., Mitani, S., Simard, M. J. and Mello, C. C. (2006). Analysis of the C. elegans Argonaute family reveals that distinct Argonautes act sequentially during RNAi. Cell 127, 747–757. doi: S0092-8674(06)01293-1 [pii] 10.1016/j.cell.2006.09.033.Google Scholar
Yoo, B. C., Kragler, F., Varkonyi-Gasic, E., Haywood, V., Archer-Evans, S., Lee, Y. M., Lough, T. J. and Lucas, W. J. (2004). A systemic small RNA signaling system in plants. Plant Cell 16, 1979–2000. doi: 10.1105/tpc.104.023614tpc.104.023614 [pii].Google Scholar
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, 25–33. doi: S0092-8674(00)80620-0 [pii] 10.1016/S0092-8674(00)80620-0.Google Scholar
Zhang, H. and Fire, A. Z. (2010). Cell autonomous specification of temporal identity by Caenorhabditis elegans microRNA lin-4. Developmental Biology 344, 603–610. doi: S0012-1606(10)00304-0 [pii] 10.1016/j.ydbio.2010.05.018.Google Scholar
Zhuang, J. J. and Hunter, C. P. (2011). Tissue-specificity of Caenorhabditis elegans Enhanced RNAi Mutants. Genetics 188, 235–237. doi: genetics.111.127209 [pii] 10.1534/genetics.111.127209.Google Scholar