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Towards full employment: using RNAi to find roles for the redundant

Oncogene volume 23, pages 8346–8352 (2004)Cite this article

Abstract

Cancer is a genetic disease that ultimately results from the failure of cells to respond correctly to diverse signals. Signal transduction and signal integration are highly complex, requiring the combinatorial interaction of multiple genes. Classical genetics in model organisms including Caenorhabditis elegans has been of immense use in identifying nonredundant components of conserved signalling pathways. However, it is likely that there is much functional redundancy in the informational processing machinery of metazoan cells; we therefore need to develop methods for uncovering such redundant functions in model organisms if we are to use them to understand complex gene interactions and oncogene cooperation. RNAi may provide a powerful tool to probe redundancy in informational networks. In this review, I set out some of the progress made so far by classical genetics in understanding redundancy in gene networks, and outline how RNAi may allow us to approach this problem more systematically in C. elegans. In particular, I discuss the use of genome-wide RNAi screens in C. elegans to identify synthetic lethal interactions and compare this with synthetic lethal interaction analysis in Saccharomyces cerevisiae.

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References

  • Ashrafi K, Chang FY, Watts JL, Fraser AG, Kamath RS, Ahringer J and Ruvkun G . (2003). Nature, 421, 268–272.

  • Beitel GJ, Clark SG and Horvitz HR . (1990). Nature, 348, 503–509.

  • Ceol CJ and Horvitz HR . (2001). Mol. Cell, 7, 461–473.

  • Chang C and Sternberg PW . (1999). Cancer Metast. Rev., 18, 203–213.

  • Chen P, Nordstrom W, Gish B and Abrams JM . (1996). Genes Dev., 10, 1773–1782.

  • Dillin A, Hsu AL, Arantes-Oliveira N, Lehrer-Graiwer J, Hsin H, Fraser AG, Kamath RS, Ahringer J and Kenyon C . (2002). Science, 298, 2398–2401.

  • Dykxhoorn DM, Novina CD and Sharp PA . (2003). Nat. Rev. Mol. Cell. Biol., 4, 457–467.

  • Fay DS, Keenan S and Han M . (2002). Genes Dev., 16, 503–517.

  • Fearon ER and Vogelstein B . (1990). Cell, 61, 759–767.

  • Ferguson EL and Horvitz HR . (1985). Genetics, 110, 17–72.

  • Ferguson EL and Horvitz HR . (1989). Genetics, 123, 109–121.

  • Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE and Mello CC . (1998). Nature, 391, 806–811.

  • Fraser AG, Kamath RS, Zipperlen P, Martinez-Campos M, Sohrmann M and Ahringer J . (2000). Nature, 408, 325–330.

  • Fraser AG and Marcotte EM . (2004). Nat. Genet., 36, 559–564.

  • Garigan D, Hsu AL, Fraser AG, Kamath RS, Ahringer J and Kenyon C . (2002). Genetics, 161, 1101–1112.

  • Giaever G, Chu AM, Ni L, Connelly C, Riles L, Veronneau S, Dow S, Lucau-Danila A, Anderson K, Andre B, Arkin AP, Astromoff A, El-Bakkoury M, Bangham R, Benito R, Brachat S, Campanaro S, Curtiss M, Davis K, Deutschbauer A, Entian KD, Flaherty P, Foury F, Garfinkel DJ, Gerstein M, Gotte D, Guldener U, Hegemann JH, Hempel S, Herman Z, Jaramillo DF, Kelly DE, Kelly SL, Kotter P, LaBonte D, Lamb DC, Lan N, Liang H, Liao H, Liu L, Luo C, Lussier M, Mao R, Menard P, Ooi SL, Revuelta JL, Roberts CJ, Rose M, Ross-Macdonald P, Scherens B, Schimmack G, Shafer B, Shoemaker DD, Sookhai-Mahadeo S, Storms RK, Strathern JN, Valle G, Voet M, Volckaert G, Wang CY, Ward TR, Wilhelmy J, Winzeler EA, Yang Y, Yen G, Youngman E, Yu K, Bussey H, Boeke JD, Snyder M, Philippsen P, Davis RW and Johnston M . (2002). Nature, 418, 387–391.

  • Gonczy P, Echeverri C, Oegema K, Coulson A, Jones SJ, Copley RR, Duperon J, Oegema J, Brehm M, Cassin E, Hannak E, Kirkham M, Pichler S, Flohrs K, Goessen A, Leidel S, Alleaume AM, Martin C, Ozlu N, Bork P and Hyman AA . (2000). Nature, 408, 331–336.

  • Gotta M and Ahringer J . (2001). Nat. Cell Biol., 3, 297–300.

  • Grether ME, Abrams JM, Agapite J, White K and Steller H . (1995). Genes Dev., 9, 1694–1708.

  • Hartman JLT, Garvik B and Hartwell L . (2001). Science, 291, 1001–1004.

  • Kamath RS, Fraser AG, Dong Y, Poulin G, Durbin R, Gotta M, Kanapin A, Le Bot N, Moreno S, Sohrmann M, Welchman DP, Zipperlen P and Ahringer J . (2003). Nature, 421, 231–237.

  • Lee SS, Lee RY, Fraser AG, Kamath RS, Ahringer J and Ruvkun G . (2003). Nat. Genet., 33, 40–48.

  • Li S, Armstrong CM, Bertin N, Ge H, Milstein S, Boxem M, Vidalain PO, Han JD, Chesneau A, Hao T, Goldberg DS, Li N, Martinez M, Rual JF, Lamesch P, Xu L, Tewari M, Wong SL, Zhang LV, Berriz GF, Jacotot L, Vaglio P, Reboul J, Hirozane-Kishikawa T, Li Q, Gabel HW, Elewa A, Baumgartner B, Rose DJ, Yu H, Bosak S, Sequerra R, Fraser A, Mango SE, Saxton WM, Strome S, Van Den Heuvel S, Piano F, Vandenhaute J, Sardet C, Gerstein M, Doucette-Stamm L, Gunsalus KC, Harper JW, Cusick ME, Roth FP, Hill DE and Vidal M . (2004). Science, 303, 540–543.

  • Lu X and Horvitz HR . (1998). Cell, 95, 981–991.

  • Lum PY, Armour CD, Stepaniants SB, Cavet G, Wolf MK, Butler JS, Hinshaw JC, Garnier P, Prestwich GD, Leonardson A, Garrett-Engele P, Rush CM, Bard M, Schimmack G, Phillips JW, Roberts CJ and Shoemaker DD . (2004). Cell, 116, 121–137.

  • Maeda I, Kohara Y, Yamamoto M and Sugimoto A . (2001). Curr. Biol., 11, 171–176.

  • Nelson DW and Padgett RW . (2003). Genes Dev., 17, 813–818.

  • Ooi SL, Shoemaker DD and Boeke JD . (2003). Nat. Genet., 35, 277–286.

  • Paradis S and Ruvkun G . (1998). Genes Dev., 12, 2488–2498.

  • Piano F, Schetter AJ, Mangone M, Stein L and Kemphues KJ . (2000). Curr. Biol., 10, 1619–1622.

  • Pothof J, van Haaften G, Thijssen K, Kamath RS, Fraser AG, Ahringer J, Plasterk RH and Tijsterman M . (2003). Genes Dev., 17, 443–448.

  • Sternberg PW and Han M . (1998). Trends Genet., 14, 466–472.

  • Su AI, Wiltshire T, Batalov S, Lapp H, Ching KA, Block D, Zhang J, Soden R, Hayakawa M, Kreiman G, Cooke MP, Walker JR and Hogenesch JB . (2004). Proc. Natl. Acad. Sci. USA, 101, 6062–6067.

  • Tong AH, Lesage G, Bader GD, Ding H, Xu H, Xin X, Young J, Berriz GF, Brost RL, Chang M, Chen Y, Cheng X, Chua G, Friesen H, Goldberg DS, Haynes J, Humphries C, He G, Hussein S, Ke L, Krogan N, Li Z, Levinson JN, Lu H, Menard P, Munyana C, Parsons AB, Ryan O, Tonikian R, Roberts T, Sdicu AM, Shapiro J, Sheikh B, Suter B, Wong SL, Zhang LV, Zhu H, Burd CG, Munro S, Sander C, Rine J, Greenblatt J, Peter M, Bretscher A, Bell G, Roth FP, Brown GW, Andrews B, Bussey H and Boone C . (2004). Science, 303, 808–813.

  • White K, Grether ME, Abrams JM, Young L, Farrell K and Steller H . (1994). Science, 264, 677–683.

  • Zipperlen P, Fraser AG, Kamath RS, Martinez-Campos M and Ahringer J . (2001). EMBO J., 20, 3984–3992.

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  1. The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK

    Andrew Fraser

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Correspondence to Andrew Fraser.

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Fraser, A. Towards full employment: using RNAi to find roles for the redundant. Oncogene 23, 8346–8352 (2004). https://doi.org/10.1038/sj.onc.1208044

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