Caenorhabditis elegans: A Model System for Anti-Cancer Drug Discovery and Therapeutic Target Identification |
Kobet, Robert A.
(Department of Medicine, Department of Oncology, Division of Hematology/Oncology, Brody School of Medicine, East Carolina University)
Pan, Xiaoping (Department of Biology, East Carolina University) Zhang, Baohong (Department of Biology, East Carolina University) Pak, Stephen C. (Department of Pediatrics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC) Asch, Adam S. (Department of Medicine, Department of Oncology, Division of Hematology/Oncology, Brody School of Medicine, East Carolina University) Lee, Myon-Hee (Department of Medicine, Department of Oncology, Division of Hematology/Oncology, Brody School of Medicine, East Carolina University) |
1 | Towatari, M., Ciro, M., Ottolenghi, S., Tsuzuki, S. and Enver, T. (2004) Involvement of mitogen-activated protein kinase in the cytokineregulated phosphorylation of transcription factor GATA-1. Hematol. J. 5, 262-272. DOI |
2 | Vaid, S., Ariz, M., Chaturbedi, A., Kumar, G. A. and Subramaniam, K. (2013) PUF-8 negatively regulates RAS/MAPK signalling to promote differentiation of C. elegans germ cells. Development 140, 1645-1654. DOI ScienceOn |
3 | Visvader, J. E. and Lindeman, G. J. (2012) Cancer stem cells: current status and evolving complexities. Cell stem cell 10, 717-728. DOI |
4 | Morgan, C. T., Lee, M. H. and Kimble, J. (2010) Chemical reprogramming of Caenorhabditis elegans germ cell fate. Nat. Chem. Biol. 6, 102-104. DOI |
5 | Nadarajan, S., Govindan, J. A., McGovern, M., Hubbard, E. J. and Greenstein, D. (2009) MSP and GLP-1/Notch signaling coordinately regulate actomyosin-dependent cytoplasmic streaming and oocyte growth in C. elegans. Development 136, 2223-2234. DOI |
6 | Nusse, R., Fuerer, C., Ching, W., Harnish, K., Logan, C., Zeng, A., ten Berge, D. and Kalani, Y. (2008) Wnt signaling and stem cell control. Cold Spring Harb. Symp. Quant. Biol. 73, 59-66. DOI |
7 | Nykamp, K., Lee, M. H. and Kimble, J. (2008) C. elegans La-related protein, LARP-1, localizes to germline P bodies and attenuates Ras-MAPK signaling during oogenesis. RNA 14, 1378-1389. DOI ScienceOn |
8 | O'Reilly, L. P., Luke, C. J., Perlmutter, D. H., Silverman, G. A. and Pak, S. C. (2014) C. elegans in high-throughput drug discovery. Adv. Drug Deliv. Rev. 69-70, 247-253. DOI |
9 | Okabe, H., Lee, S. H., Phuchareon, J., Albertson, D. G., McCormick, F. and Tetsu, O. (2006) A critical role for FBXW8 and MAPK in cyclin D1 degradation and cancer cell proliferation. PLoS One 1, e128. DOI |
10 | Pepper, A. S., Killian, D. J. and Hubbard, E. J. (2003a) Genetic analysis of Caenorhabditis elegans glp-1 mutants suggests receptor interaction or competition. Genetics 163, 115-132. |
11 | Pepper, A. S., Lo, T. W., Killian, D. J., Hall, D. H. and Hubbard, E. J. (2003b) The establishment of Caenorhabditis elegans germline pattern is controlled by overlapping proximal and distal somatic gonad signals. Dev. Biol. 259, 336-350. DOI |
12 | Petcherski, A. G. and Kimble, J. (2000) LAG-3 is a putative transcriptional activator in the C. elegans Notch pathway. Nature 405, 364-368. DOI |
13 | Phillips, B. T., Kidd, A. R., 3rd, King, R., Hardin, J. and Kimble, J. (2007) Reciprocal asymmetry of SYS-1/beta-catenin and POP-1/ TCF controls asymmetric divisions in Caenorhabditis elegans. Proc. Natl. Acad. Sci. U.S.A. 104, 3231-3236. DOI |
14 | Reedijk, M. (2012) Notch signaling and breast cancer. Adv. Exp. Med. Biol. 727, 241-257. DOI ScienceOn |
15 | Reya, T. and Clevers, H. (2005) Wnt signalling in stem cells and cancer. Nature 434, 843-850. DOI ScienceOn |
16 | Ristorcelli, E. and Lombardo, D. (2010) Targeting Notch signaling in pancreatic cancer. Expert Opin. Ther. Targets 14, 541-552. DOI |
17 | Saxena, N., Lahiri, S. S., Hambarde, S. and Tripathi, R. P. (2008) RAS: target for cancer therapy. Cancer Invest. 26, 948-955. DOI |
18 | Lee, M. H., Cha, D. S., Mamillapalli, S. S., Kwon, Y. C. and Koo, H. S. (2014) Transgene-mediated co-suppression of DNA topoisomerase-1 gene in Caenorhabditis elegans. Int. Biochem. Mol. Biol. 5, 11-20. |
19 | Lee, M. H., Ohmachi, M., Arur, S., Nayak, S., Francis, R., Church, D., Lambie, E. and Schedl, T. (2007b) Multiple functions and dynamic activation of MPK-1 extracellular signal-regulated kinase signaling in Caenorhabditis elegans germline development. Genetics 177, 2039-2062. DOI |
20 | Lee, M. H., Hook, B., Lamont, L. B., Wickens, M. and Kimble, J. (2006) LIP-1 phosphatase controls the extent of germline proliferation in Caenorhabditis elegans. EMBO J. 25, 88-96. DOI |
21 | Lino, M. M., Merlo, A. and Boulay, J. L. (2010) Notch signaling in glioblastoma: a developmental drug target? BMC Med. 8, 72. DOI |
22 | Liu, J., Sato, C., Cerletti, M. and Wagers, A. (2010) Notch signaling in the regulation of stem cell self-renewal and differentiation. Curr. Top. Dev. Biol. 92, 367-409. DOI |
23 | Lomenick, B., Hao, R., Jonai, N., Chin, R. M., Aghajan, M., Warburton, S., Wang, J., Wu, R. P., Gomez, F., Loo, J. A., Wohlschlegel, J. A., Vondriska, T. M., Pelletier, J., Herschman, H. R., Clardy, J., Clarke, C. F. and Huang, J. (2009) Target identification using drug affinity responsive target stability (DARTS). Proc. Natl. Acad. Sci. U.S.A. 106, 21984-21989. DOI ScienceOn |
24 | Lomenick, B., Jung, G., Wohlschlegel, J. A. and Huang, J. (2011) Target identification using drug affinity responsive target stability (DARTS). Curr. Protoc. Chem. Biol. 3, 163-180. |
25 | Lopez, A. L., 3rd, Chen, J., Joo, H. J., Drake, M., Shidate, M., Kseib, C. and Arur, S. (2013) DAF-2 and ERK couple nutrient availability to meiotic progression during Caenorhabditis elegans oogenesis. Dev. Cell 27, 227-240. DOI |
26 | Lublin, A. L. and Link, C. D. (2013) Alzheimer's disease drug discovery: in vivo screening using Caenorhabditis elegans as a model for beta-amyloid peptide-induced toxicity. Drug Discov. Today Technol. 10, e115-119. DOI |
27 | Moon, B. S., Jeong, W. J., Park, J., Kim, T. I., Min do, S. and Choi, K. Y. (2014) Role of oncogenic K-Ras in cancer stem cell activation by aberrant Wnt/beta-catenin signaling. J. Natl. Cancer Inst. 106, djt373. DOI |
28 | Maine, E. M. and Kimble, J. (1989) Identification of genes that interact with glp-1, a gene required for inductive cell interactions in Caenorhabditis elegans. Development 106, 133-143. |
29 | Marshall, M. (1995) Interactions between Ras and Raf: key regulatory proteins in cellular transformation. Mol. Reprod. Dev. 42, 493-499. DOI |
30 | Miyamoto, S. and Rosenberg, D. W. (2011) Role of Notch signaling in colon homeostasis and carcinogenesis. Cancer Sci. 102, 1938-1942. DOI ScienceOn |
31 | Ferrando, A. A. (2009) The role of NOTCH1 signaling in T-ALL. Hematology Am. Soc. Hematol. Educ. Program, 353-361. |
32 | Galluzzo, P. and Bocchetta, M. (2011) Notch signaling in lung cancer. Expert Rev. Anticancer Ther. 11, 533-540. DOI |
33 | Greenwald, I. (2005) LIN-12/Notch signaling in C. elegans. Worm-Book, 1-16. |
34 | Hajnal, A. and Berset, T. (2002) The C. elegans MAPK phosphatase LIP-1 is required for the G(2)/M meiotic arrest of developing oocytes. EMBO J. 21, 4317-4326. DOI |
35 | Hara, M. and Han, M. (1995) Ras farnesyltransferase inhibitors suppress the phenotype resulting from an activated ras mutation in Caenorhabditis elegans. Proc. Natl. Acad. Sci. U.S.A. 92, 3333-3337. DOI |
36 | He, T. C., Sparks, A. B., Rago, C., Hermeking, H., Zawel, L., da Costa, L. T., Morin, P. J., Vogelstein, B. and Kinzler, K. W. (1998) Identification of c-MYC as a target of the APC pathway. Science 281, 1509-1512. DOI ScienceOn |
37 | James, R. G., Conrad, W. H. and Moon, R. T. (2008) Beta-cateninindependent Wnt pathways: signals, core proteins, and effectors. Methods Mol. Biol. 468, 131-144. DOI ScienceOn |
38 | Henderson, S. T., Gao, D., Lambie, E. J. and Kimble, J. (1994) lag-2 may encode a signaling ligand for the GLP-1 and LIN-12 receptors of C. elegans. Development 120, 2913-2924. |
39 | Holland, J. D., Klaus, A., Garratt, A. N. and Birchmeier, W. (2013) Wnt signaling in stem and cancer stem cells. Curr. Opin. Cell Biol. 25, 254-264. DOI |
40 | Hughes, D. P. (2009) How the NOTCH pathway contributes to the ability of osteosarcoma cells to metastasize. Cancer Treat. Res. 152, 479-496. DOI |
41 | Katoh, M. (2008) WNT signaling in stem cell biology and regenerative medicine. Curr. Drug Targets 9, 565-570. DOI ScienceOn |
42 | Kidd, A. R., 3rd, Miskowski, J. A., Siegfried, K. R., Sawa, H. and Kimble, J. (2005) A beta-catenin identified by functional rather than sequence criteria and its role in Wnt/MAPK signaling. Cell 121, 761-772. DOI ScienceOn |
43 | Kimble, J. and Crittenden, S. L. (2005) Germline proliferation and its control. WormBook, 1-14. |
44 | Kimble, J. and Crittenden, S. L. (2007) Controls of germline stem cells, entry into meiosis, and the sperm/oocyte decision in Caenorhabditis elegans. Annu. Rev. Cell Dev. Biol. 23, 405-433. DOI |
45 | Lackner, M. R. and Kim, S. K. (1998) Genetic analysis of the Caenorhabditis elegans MAP kinase gene mpk-1. Genetics 150, 103-117. |
46 | Lam, N., Chesney, M. A. and Kimble, J. (2006) Wnt signaling and CEH-22/tinman/Nkx2.5 specify a stem cell niche in C. elegans. Curr. Biol. 16, 287-295. DOI ScienceOn |
47 | Byrd, D. T., Knobel, K., Affeldt, K., Crittenden, S. L. and Kimble, J. (2014) A DTC niche plexus surrounds the germline stem cell pool in Caenorhabditis elegans. PloS One 9, e88372. DOI |
48 | Lamont, L. B., Crittenden, S. L., Bernstein, D., Wickens, M. and Kimble, J. (2004) FBF-1 and FBF-2 regulate the size of the mitotic region in the C. elegans germline. Dev. Cell 7, 697-707. DOI |
49 | Blelloch, R. and Kimble, J. (1999) Control of organ shape by a secreted metalloprotease in the nematode Caenorhabditis elegans. Nature 399, 586-590. DOI |
50 | Byrd, D. T. and Kimble, J. (2009) Scratching the niche that controls Caenorhabditis elegans germline stem cells. Semin. Cell Dev. Biol. 20, 1107-1113. DOI ScienceOn |
51 | Cha, D. S., Datla, U. S., Hollis, S. E., Kimble, J. and Lee, M. H. (2012) The Ras-ERK MAPK regulatory network controls dedifferentiation in Caenorhabditis elegans germline. Biochim. Biophys. Acta 1823, 1847-1855. DOI |
52 | Chen, P. H., Chen, X., Lin, Z., Fang, D. and He, X. (2013) The structural basis of R-spondin recognition by LGR5 and RNF43. Genes Dev. 27, 1345-1350. DOI |
53 | Datla, U. S., Scovill, N. C., Brokamp, A. J., Kim, E., Asch, A. S. and Lee, M. H. (2014) Role of PUF-8/PUF protein in stem cell control, sperm-oocyte decision and cell fate reprogramming. J. Cell. Physiol. 229, 1306-1311. DOI |
54 | Fan, X., Matsui, W., Khaki, L., Stearns, D., Chun, J., Li, Y. M. and Eberhart, C. G. (2006) Notch pathway inhibition depletes stem-like cells and blocks engraftment in embryonal brain tumors. Cancer Res. 66, 7445-7452. DOI |
55 | Duncia, J. V., Santella, J. B., 3rd, Higley, C. A., Pitts, W. J., Wityak, J., Frietze, W. E., Rankin, F. W., Sun, J. H., Earl, R. A., Tabaka, A. C., Teleha, C. A., Blom, K. F., Favata, M. F., Manos, E. J., Daulerio, A. J., Stradley, D. A., Horiuchi, K., Copeland, R. A., Scherle, P. A., Trzaskos, J. M., Magolda, R. L., Trainor, G. L., Wexler, R. R., Hobbs, F. W. and Olson, R. E. (1998) MEK inhibitors: the chemistry and biological activity of U0126, its analogs, and cyclization products. Bioorg. Med. Chem. Lett. 8, 2839-2844. DOI ScienceOn |
56 | Eisenmann, D. M. (2005) Wnt signaling. WormBook 1-17. |
57 | Ewbank, J. J. and Zugasti, O. (2011) C. elegans: model host and tool for antimicrobial drug discovery. Dis. Model Mech. 4, 300-304. DOI |
58 | Favata, M. F., Horiuchi, K. Y., Manos, E. J., Daulerio, A. J., Stradley, D. A., Feeser, W. S., Van Dyk, D. E., Pitts, W. J., Earl, R. A., Hobbs, F., Copeland, R. A., Magolda, R. L., Scherle, P. A. and Trzaskos, J. M. (1998) Identification of a novel inhibitor of mitogen-activated protein kinase kinase. J. Biol. Chem. 273, 18623-18632. DOI ScienceOn |
59 | Feng, Z., Li, W., Ward, A., Piggott, B. J., Larkspur, E. R., Sternberg, P. W. and Xu, X. Z. (2006) A C. elegans model of nicotine-dependent behavior: regulation by TRP-family channels. Cell 127, 621-633. DOI |
60 | Allenspach, E. J., Maillard, I., Aster, J. C. and Pear, W. S. (2002) Notch signaling in cancer. Cancer Biol. Ther. 1, 466-476. DOI |
61 | Anastassopoulou, C. G., Fuchs, B. B. and Mylonakis, E. (2011) Caenorhabditis elegans-based model systems for antifungal drug discovery. Curr. Pharm. Des. 17, 1225-1233. DOI |
62 | Artavanis-Tsakonas, S., Rand, M. D. and Lake, R. J. (1999) Notch signaling: cell fate control and signal integration in development. Science 284, 770-776. DOI ScienceOn |
63 | Avila, J. L. and Kissil, J. L. (2013) Notch signaling in pancreatic cancer: oncogene or tumor suppressor? Trends Mol. Med. 19, 320-327. DOI |
64 | Abel, E. V., Kim, E. J., Wu, J., Hynes, M., Bednar, F., Proctor, E., Wang, L., Dziubinski, M. L. and Simeone, D. M. (2014). The Notch pathway is important in maintaining the cancer stem cell population in pancreatic cancer. PLoS One 9, e91983. DOI |
65 | Ahn, D., Cha, D. S., Lee, E. B., Kim, B. J., Lee, S. Y., Jeon, H., Ahn, M. S., Lim, H. W., Lee, H. Y. and Kim, D. K. (2013) The longevity properties of 1,2,3,4,6-Penta-O-Galloyl-beta-D-Glucose from Curcuma longa in Caenorhabditis elegans. Biomol. Ther. 21, 442-446. DOI |
66 | Benson, J. A., Cummings, E. E., O'Reilly, L. P., Lee, M. H. and Pak, S. C. (2014) A high-content assay for identifying small molecules that reprogram C. elegans germ cell fate. Methods 68, 529-535. DOI |
67 | Bae, Y. K., Sung, J. Y., Kim, Y. N., Kim, S., Hong, K. M., Kim, H. T., Choi, M. S., Kwon, J. Y. and Shim, J. (2012) An in vivo C. elegans model system for screening EGFR-inhibiting anti-cancer drugs. PLoS One 7, e42441. DOI |
68 | Bao, B., Wang, Z., Ali, S., Kong, D., Li, Y., Ahmad, A., Banerjee, S., Azmi, A. S., Miele, L. and Sarkar, F. H. (2011) Notch-1 induces epithelial-mesenchymal transition consistent with cancer stem cell phenotype in pancreatic cancer cells. Cancer Lett. 307, 26-36. DOI ScienceOn |
69 | Beitel, G. J., Clark, S. G. and Horvitz, H. R. (1990) Caenorhabditis elegans ras gene let-60 acts as a switch in the pathway of vulval induction. Nature 348, 503-509. DOI |
70 | Berry, L. W., Westlund, B. and Schedl, T. (1997) Germ-line tumor formation caused by activation of glp-1, a Caenorhabditis elegans member of the Notch family of receptors. Development 124, 925-936. |
71 | Berset, T., Hoier, E. F., Battu, G., Canevascini, S. and Hajnal, A. (2001) Notch inhibition of RAS signaling through MAP kinase phosphatase LIP-1 during C. elegans vulval development. Science 291, 1055-1058. DOI |
72 | Birchmeier, W. (2011) Stem cells: Orphan receptors find a home. Nature 476, 287-288. DOI ScienceOn |
73 | Blelloch, R., Anna-Arriola, S. S., Gao, D., Li, Y., Hodgkin, J. and Kimble, J. (1999) The gon-1 gene is required for gonadal morphogenesis in Caenorhabditis elegans. Dev. Biol. 216, 382-393. DOI |
74 | Wang, D., Huang, B., Zhang, S., Yu, X., Wu, W. and Wang, X. (2013) Structural basis for R-spondin recognition by LGR4/5/6 receptors. Genes Dev. 27, 1339-1344. DOI |
75 | Zhao, Y., Bjorbaek, C. and Moller, D. E. (1996) Regulation and interaction of pp90(rsk) isoforms with mitogen-activated protein kinases. J. Biol. Chem. 271, 29773-29779. DOI |
76 | Wend, P., Holland, J. D., Ziebold, U. and Birchmeier, W. (2010) Wnt signaling in stem and cancer stem cells. Semin. Cell Dev. Biol. 21, 855-863. DOI ScienceOn |
77 | Whelan, J. T., Hollis, S. E., Cha, D. S., Asch, A. S. and Lee, M. H. (2012) Post-transcriptional regulation of the Ras-ERK/MAPK signaling pathway. J. Cell. Physiol. 227, 1235-1241. DOI |
78 | Yoo, A. S., Bais, C. and Greenwald, I. (2004) Crosstalk between the EGFR and LIN-12/Notch pathways in C. elegans vulval development. Science 303, 663-666. DOI |
79 | Schouest, K. R., Kurasawa, Y., Furuta, T., Hisamoto, N., Matsumoto, K. and Schumacher, J. M. (2009) The germinal center kinase GCK-1 is a negative regulator of MAP kinase activation and apoptosis in the C. elegans germline. PLoS One 4, e7450. DOI |
80 | Schulze, W. X., Deng, L. and Mann, M. (2005) Phosphotyrosine interactome of the ErbB-receptor kinase family. Mol. Syst. Biol. 1, 2005 0008. |
81 | Sellings, L., Pereira, S., Qian, C., Dixon-McDougall, T., Nowak, C., Zhao, B., Tyndale, R. F. and van der Kooy, D. (2013) Nicotine-motivated behavior in Caenorhabditis elegans requires the nicotinic acetylcholine receptor subunits acr-5 and acr-15. Eur. J. Neurosci. 37, 743-756. DOI |
82 | Siegfried, K. R. and Kimble, J. (2002) POP-1 controls axis formation during early gonadogenesis in C. elegans. Development 129, 443-453. |
83 | Sundaram, M. V. (2006) RTK/Ras/MAPK signaling. WormBook, 1-19. |
84 | Smith, M. A., Jr., Zhang, Y., Polli, J. R., Wu, H., Zhang, B., Xiao, P., Farwell, M. A. and Pan, X. (2013) Impacts of chronic low-level nicotine exposure on Caenorhabditis elegans reproduction: identification of novel gene targets. Reprod. Toxicol. 40, 69-75. DOI |
85 | Squiban, B. and Kurz, C. L. (2011) C. elegans: an all in one model for antimicrobial drug discovery. Curr. Drug Targets 12, 967-977. DOI |
86 | Sun, W., Gaykalova, D. A., Ochs, M. F., Mambo, E., Arnaoutakis, D., Liu, Y., Loyo, M., Agrawal, N., Howard, J., Li, R., Ahn, S., Fertig, E., Sidransky, D., Houghton, J., Buddavarapu, K., Sanford, T., Choudhary, A., Darden, W., Adai, A., Latham, G., Bishop, J., Sharma, R., Westra, W. H., Hennessey, P., Chung, C. H. and Califano, J. A. (2014) Activation of the NOTCH pathway in head and neck cancer. Cancer Res. 74, 1091-1104. DOI ScienceOn |
87 | Taki, F. A., Pan, X. and Zhang, B. (2014) Chronic nicotine exposure systemically alters microRNA expression profiles during postembryonic stages in Caenorhabditis elegans. J. Cell. Physiol. 229, 79-89. |
88 | Tamura, Y., Simizu, S. and Osada, H. (2004) The phosphorylation status and anti-apoptotic activity of Bcl-2 are regulated by ERK and protein phosphatase 2A on the mitochondria. FEBS Lett. 569, 249-255. DOI ScienceOn |
89 | Tetsu, O. and McCormick, F. (1999) Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 398, 422-426. DOI ScienceOn |
90 | Tilmann, C. and Kimble, J. (2005) Cyclin D regulation of a sexually dimorphic asymmetric cell division. Dev. Cell 9, 489-499. DOI |
91 | Kershner, A. M., Shin, H., Hansen, T. J. and Kimble, J. (2014) Discovery of two GLP-1/Notch target genes that account for the role of GLP-1/Notch signaling in stem cell maintenance. Proc. Natl. Acad. Sci. U.S.A. 111, 3739-3744. DOI |
92 | Chamorro, M. N., Schwartz, D. R., Vonica, A., Brivanlou, A. H., Cho, K. R. and Varmus, H. E. (2005) FGF-20 and DKK1 are transcriptional targets of beta-catenin and FGF-20 is implicated in cancer and development. EMBO J. 24, 73-84. DOI |
93 | Eckmann, C. R., Kraemer, B., Wickens, M. and Kimble, J. (2002) GLD-3, a bicaudal-C homolog that inhibits FBF to control germline sex determination in C. elegans. Dev. Cell 3, 697-710. DOI |
94 | Austin, J. and Kimble, J. (1987) glp-1 is required in the germ line for regulation of the decision between mitosis and meiosis in C. elegans. Cell 51, 589-599. DOI ScienceOn |
95 | Pennica, D., Swanson, T. A., Welsh, J. W., Roy, M. A., Lawrence, D. A., Lee, J., Brush, J., Taneyhill, L. A., Deuel, B., Lew, M., Watanabe, C., Cohen, R. L., Melhem, M. F., Finley, G. G., Quirke, P., Goddard, A. D., Hillan, K. J., Gurney, A. L., Botstein, D. and Levine, A. J. (1998) WISP genes are members of the connective tissue growth factor family that are up-regulated in wnt-1-transformed cells and aberrantly expressed in human colon tumors. Proc. Natl. Acad. Sci. U.S.A. 95, 14717-14722. DOI |
96 | Lee, M. H., Hook, B., Pan, G., Kershner, A. M., Merritt, C., Seydoux, G., Thomson, J. A., Wickens, M. and Kimble, J. (2007a) Conserved regulation of MAP kinase expression by PUF RNA-binding proteins. PLoS Genet. 3, e233. DOI |